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Sample records for anti-thyroid antibodies effects

  1. Anti-thyroid peroxidase antibodies: Its effect on thyroid gland and breast tissue

    OpenAIRE

    Sabitha Kandi; Pragna Rao

    2012-01-01

    Thyroid peroxidase (TPO) is a key enzyme in the synthesis of thyroid hormone. TPO is involved in thyroid hormone synthesis (organification and coupling reactions). TPO is a major antigen corresponding to thyroid-microsomal autoantibodies. Anti-TPO auto antibodies are very important to diagnose autoimmune thyroid diseases and also in estimating its clinical course. Autoimmune thyroid disease is detected mostly by measuring circulating antibodies to thyroglobulin which is uncommon measurement o...

  2. Anti-thyroid peroxidase antibodies: Its effect on thyroid gland and breast tissue

    Directory of Open Access Journals (Sweden)

    Sabitha Kandi

    2012-01-01

    Full Text Available Thyroid peroxidase (TPO is a key enzyme in the synthesis of thyroid hormone. TPO is involved in thyroid hormone synthesis (organification and coupling reactions. TPO is a major antigen corresponding to thyroid-microsomal autoantibodies. Anti-TPO auto antibodies are very important to diagnose autoimmune thyroid diseases and also in estimating its clinical course. Autoimmune thyroid disease is detected mostly by measuring circulating antibodies to thyroglobulin which is uncommon measurement of antibodies to TPO that gives reliable information about autoimmune thyroid disease. Eighty percent of Grave′s disease patients have high levels of antiTPO antibodies. About 4% of subclinical hypothyroid patients with positive TPO antibodies develop clinical hypothyroidism. There is always a controversy on the relationship between breast cancer and thyroid disorders. As these tissues, i.e., breast and thyroid, originate embryologically from the same type of cells, hypothyroid/hyperthyroid females are more prone to develop benign or malignant breast tumors. The studies on breast cancer patients indicate increased thyroid disorders in breast cancer patients, most commonly Hashimoto′s thyroiditis accounts to increased thyroid disorders in these patients. This is independent of hormonal receptor status of the patient. These findings suggest the usefulness of screening for thyroid disease in any patient with breast cancer.

  3. Frequency of anti thyroid peroxidase antibody in patients of vitiligo

    International Nuclear Information System (INIS)

    Objective: The objective of this study was to compare the frequency of anti thyroid peroxidase antibody in patients suffering from vitiligo with healthy control group. Type of Study: Case control study. Settings: Dermatology Department, Military Hospital, Rawalpindi, from 20th March 2010 to 20th July 2011. Material and Methods: Fifty clinically diagnosed patients of vitiligo, age = 18 yrs and both genders with no history of thyroid disease, past or current use of drugs for thyroid disorder or thyroid surgery were included as cases (Group A). Fifty healthy individuals with no evidence of vitiligo or thyroid disorder on history and physical examination and with no family history of vitiligo, matched for age and gender with cases, were included as control (Group B). Serum anti thyroid peroxidase (anti TPO) antibodies were measured using enzyme linked immunosorbent assay (ELISA) in both cases and control. Results: Eight (16%) patients in Group A were anti-thyroid peroxidase antibody positive and forty two (84%) patients were negative while one (2%) patient was anti-thyroid peroxidase antibody positive in Group B and forty nine (98%) patients were negative (p = 0.001). Conclusion: Anti TPO antibody is significantly more common in patients of vitiligo as compared to general population. (author)

  4. High frequency of positive anti-thyroid peroxidase antibodies (ATPO) in adult subjects without known thyroid disease, Santiago de Chile

    International Nuclear Information System (INIS)

    Background: Anti-thyroid peroxidase antibodies have a pathogenic role in Hashimoto thyroiditis. Between 10 and 19% of individuals without thyroid disease, have positive titers of these antibodies. Aim: To study the frequency of positive titers of anti-thyroid peroxidase antibodies in healthy individuals. Material and Methods: A blood sample, to measure anti-thyroid peroxidase antibodies and thyroid stimulating hormone (TSH) by chemiluminescence assay, was obtained from 67 women and 62 men aged 45 ± 14 years, without a personal or familiar history of thyroid diseases and normal thyroid palpation. The cutoff point of the manufacturer to consider positive a titer of anti-thyroid peroxidase antibodies was set at 35 IU/ml. Results: Twenty-eight women and 28 men had positive antibody titers (43% of the sample). Subjects in the upper tercile of anti-thyroid peroxidase antibody titers had a higher TSH than those in the second tercile, although within normal limits (1.73 ± 0.74 and 1.37 ± 0.59 mlU/L, respectively p = 0.02) Conclusions: Forty three percent of the studied subjects without personal or familial history of thyroid diseases had positive titers of anti-thyroid peroxidase antibodies. Further prospective studies should evaluate whether this observation discloses an increase in thyroid autoimmune disease in a population with increased iodine intake

  5. Association between anti-thyroid peroxidase antibody and asthma in women.

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    Mitra Samareh Fekri

    2012-09-01

    Full Text Available About 8% of the general population suffers from autoimmune diseases, from which 78% are women. One of the most important causes of thyroid diseases is autoimmunity in origin, and it seems that people with thyroid diseases present more signs of asthma. This study was therefore designed to investigate the frequency of autoimmune thyroid diseases in women suffering from bronchial asthma.In a cross-sectional study, 100 women with asthma and 100 women as control group were tested for thyroid function and anti-thyroid peroxidase antibody (anti-TPO Ab measurements.  The  asthmatic  patients  were  selected  based  on  having  chronic  cough, dyspnea, wheezing and clinical examination of the chest. The diagnosis was confirmed by pulmonary function tests. Blood tests were done by electrochemiluminescence immunoassay method.No hyperthyroid patient was found in either group. Serum TSH and Total T4 levels were not statistically different between the two groups, but serum anti-TPO Ab levels in women with asthma (74±13.6  IU/ml  was significantly higher than  control  group  (45.24±10.56 IU/ml. After adjusting the effect of age and BMI, the relationship between asthma and anti- TPO Ab (>50 IU/ml was statistically significant (OR=3.3, P<0.01.Positive anti-TPO Ab in asthmatic patients may show presence of a hidden autoimmune thyroiditis in these patients. We suggested checking asthmatic patients for thyroid diseases.

  6. Lack of a role for cross-reacting anti-thyroid antibodies in chronic idiopathic urticaria.

    Science.gov (United States)

    Mozena, Jonathan D; Tiñana, Adrienne; Negri, Julie; Steinke, John W; Borish, Larry

    2010-07-01

    The etiology of chronic idiopathic urticaria (CIU) is attributed to autoantibodies directed against the alpha-chain of the high-affinity IgE receptor (FcepsilonRIalpha) or IgE on mast cells in 30-60% of patients. Approximately 30% of CIU patients have Hashimoto's thyroiditis (HT). We investigated the pathophysiologic relationship of anti-thyroid and anti-FcepsilonRIalpha antibodies. Nine individuals with both CIU and HT underwent autologous serum skin testing (ASST) and sera were assayed for thyroid autoantibodies, thyroid-stimulating hormone, and anti-FcepsilonRIalpha antibodies. Serum samples were studied for their ability to activate a human mast cell line (LUVA) as determined by cysteinyl leukotriene (CysLT) production. Experiments were performed to determine whether epitope cross-reactivity could explain the high incidence of HT found in CIU patients. A significant proportion of CIU patients had a positive ASST (nine of six) and anti-FcepsilonRIalpha antibodies (six of nine). Incubation of patient sera with FcepsilonRIalpha, but not thyroglobulin or thyroid peroxidase, resulted in the decreased ability to detect anti-FcepsilonRIalpha antibodies. Incubation with thyroid antigens did not inhibit CysLT production by mast cells. Epitopic cross-reactivity does not explain the increased prevalence of HT found in CIU patients. The frequent concurrence of HT and CIU likely reflects a genetic tendency toward autoimmune diseases. PMID:20182447

  7. Immuno-localisation of anti-thyroid antibodies in adult human cerebral cortex.

    Science.gov (United States)

    Moodley, Kogie; Botha, Julia; Raidoo, Deshandra Munsamy; Naidoo, Strinivasen

    2011-03-15

    Expression of thyroid-stimulating hormone receptor (TSH-R) has been demonstrated in adipocytes, lymphocytes, bone, kidney, heart, intestine and rat brain. Immuno-reactive TSH-R has been localised in rat brain and human embryonic cerebral cortex but not in adult human brain. We designed a pilot study to determine whether anti-thyroid auto-antibodies immuno-localise in normal adult human cerebral cortex. Forensic samples from the frontal, motor, sensory, occipital, cingulate and parieto-occipito-temporal association cortices were obtained from five individuals who had died of trauma. Although there were no head injuries, the prior psychiatric history of patients was unknown. The tissues were probed with commercial antibodies against both human TSH-R and human thyroglobulin (TG). Anti-TSH-R IgG immuno-localised to cell bodies and axons of large neurones in all 6 regions of all 5 brains. The intensity and percentage of neurones labelled were similar in all tissue sections. TSH-R immuno-label was also observed in vascular endothelial cells in the cingulate gyrus. Although also found in all 5 brains and all six cortical regions, TG localised exclusively in vascular smooth muscle cells and not on neurones. Although limited by the small sample size and number of brain areas examined, this is the first study describing the presence of antigenic targets for anti-TSH-R IgG on human cortical neurons, and anti-TG IgG in cerebral vasculature. PMID:21196016

  8. Subacute cognitive deterioration with high serum anti-thyroid peroxidase antibodies: two cases and a plea for pragmatism.

    Science.gov (United States)

    Segers, Kurt; Braconnier, Philippe; Corazza, Francis; Divano, Luisa; Mabrouk, Asmaa; Robberecht, Jean; Surquin, Murielle

    2013-09-01

    Autoimmune encephalopathy is a rare but potentially reversible cause of cognitive deterioration and neuropsychiatric disturbances. We describe two older female patients with subacute cognitive decline and marked neuropsychiatric disturbances in the presence of high serum anti-thyroid peroxidase antibodies and with normal dosage of free thyroxine 4. One patient recovered almost completely after oral corticotherapy. Differential diagnosis and the role of biomarkers, in particular, are discussed. We support a pragmatic approach involving a short empirical therapeutic trial with intravenous or oral corticoids; this should be considered in all patients with subacute encephalopathy and with laboratory arguments for an underlying autoimmune aetiology. PMID:25913766

  9. Thyroid Function and Anti-Thyroid Antibodies in Iranian Patients with Type 1 Diabetes Mellitus: Influences of Age and Sex

    Directory of Open Access Journals (Sweden)

    Faranak Sharifi

    2008-03-01

    Full Text Available Type 1 diabetes mellitus is frequently associated with autoimmune thyroid disease (ATD.Genetic susceptibility for autoantibody formation in association with ATD and type 1 diabetes mellitus has been described with varying frequencies, but there is still debate about its prevailing situation in Iran. We have therefore investigated the prevalence of anti-thyroid peroxidase (anti-TPO and anti thyroglubolin (Anti TG antibodies in type 1 diabetic patients, and compared the effect of age and sex on the thyroid autoimmunity in patients with type 1 diabetes mellitus in Iran.Ninety one subjects with type 1 diabetes mellitus and one hundred and sixty three unrelated normal controls under the age of thirty years were recruited for the detection of anti-TPO and anti-TG. Radio Immuno Assay and chemiluminescence methods were used for anti-TPO and anti-TG detection respectively.Among 91 type 1 diabetic patients, 36 (39.6% were positive for anti-TPO and 27(30% were positive for antiTG. Anti-TPO antibodies were detected only in 6.7% of control group. Comparing with those without thyroid autoimmunity, there was a female preponderance for the type 1 diabetic patients with thyroid autoimmunity (female: male, 28:14 vs. 28:20 respectively. Among the type 1 diabetic patients those with thyroid autoimmunity, tended to be older (p: 0.04 and to have higher TSH concentration (p: 0.03. Patients with high anti-TPO levels had longer duration of diabetes (P: 0.02.The presence of anti-TPO in 39.6% of our type 1 diabetic patients comparing with 8.5% of normal subjects confirmed the strong association of ATD and type 1 diabetes mellitus.

  10. Anti-Thyroid Peroxidase Antibodies and Male Gender Are Associated with Diabetes Occurrence in Patients with Beta-Thalassemia Major

    Science.gov (United States)

    Pes, Giovanni M.; Tolu, Francesco; Dore, Maria P.

    2016-01-01

    Background. Intensive transfusion schedule and iron-chelating therapy prolonged and improved quality of life in patients with β-thalassemia (β-T) major. However, this led to an increased risk of developing impaired glucose tolerance or diabetes. In this study we analyzed variables associated with the occurrence of impaired glucose tolerance or diabetes in patients with β-T major. Methods. 388 Sardinian patients were included. Age, gender, duration of chelation therapy, body mass index, and markers of pancreatic and extrapancreatic autoimmunity were analyzed. Results. Multiple logistic regression analysis showed that anti-thyroid peroxidase (TPO) antibodies (Ab) (OR = 3.36; p = 0.008) and male gender (OR = 1.98; p = 0.025) were significantly associated with glucose impairment, while the other variables were not. Ferritin levels were significantly higher in TPOAb positive compared to TPOAb negative patients (4870 ± 1665 μg/L versus 2922 ± 2773 μg/L; p < 0.0001). Conclusions. In patients with β-T major a progressive damage of insulin-producing cells due to secondary hemosiderosis appears to be the most reasonable mechanism associated with glucose metabolism disorders. The findings need to be confirmed with additional well designed studies to address the question of whether TPOAb may have a role in the management of these patients. PMID:27123460

  11. ANTI-THYROID PEROXIDASE ANTIBODY LEVEL IN THYROID NODULES: WITH SPECIAL REFERENCE TO THYROID NEOPLASIA

    Directory of Open Access Journals (Sweden)

    Bera Swati

    2013-06-01

    Full Text Available Anti-TPO antibody level was evaluated in 86 patients, along with 25 healthy controls to detect its change in various forms of thyroid nodules particularly in thyroid malignancy when compared with healthy controls. The study revealed that Anti-TPO antibody level was increased in Benign & toxic form of Multi nodular goiter and papillary carcinoma but there is no elevation of Anti- TPO antibody level in follicular adenoma or follicular carcinoma.

  12. The anti-thyroid antibody and I-131 uptake in thyroid disorder patient

    International Nuclear Information System (INIS)

    The problem of thyroid disorder is extensive in Bangladesh, even more than that of other developing countries. The high incidence rate of goiter is reduced after universal iodine supplement. This study has been undertaken to study the an-thyroid anti-body level among the thyroid disorder population (anti-TPO and anti-thyrogobulin antibody) and TSAb among Graves' disease and sub-acute thyroiditis. This study was performed over 300 persons of them 150 have some type of thyroid (patient) disorder and 150 have got no clinical thyroid disorder (volunteer). We also studied TSH receptor anti-body (TSAb) in 112 Graves' disease patients and 86 patients with sub-acute thyroiditis. All the patient had I-131 Uptake in 24 hours. Among the patient 42(28%) had elevated anti-TPO, 12(8%) had borderline and 96(64%) had normal anti-TPO. It was found the uptake percentage of this group of patient hade slight lower than average uptake of our population. 13±5% It was found that 28(18.6%) had elevated anti thyrogobulin anti-body, 9 (6.2%) had borderline and 113(75.3%) had normal level anti thyrogobulin anti-body. It was also that found the uptake percentage of this group of patient had slight lower than average uptake of our population. We also found that 21% patient had elevated both the antibodies. Among the normal volunteer 24(16%) had elevated anti-TPO, 8 (5.3%) had borderline and 118(78.7%) had normal level of anti-TPO. Thyroid 1-131 uptake was 15±4%. It was found that 14(9.3%) had elevated anti thyrogobulin anti-body, 6(4.1%) had borderline and 130 (76.6%) had normal level of anti thyrogobulin anti-body. Among the normal volunteer 6% had elevated both the antibodies. It was found 91% patient Graves' disease had positive TSAb and 92% of' sub-acute thyroiditis has negative TSAb, I-131 uptake was 31±8% among this group of patient.. Thyroid stimulating antibody is found in 91% of Graves' disease and very few patient with sub-acute thyroiditis. The uptake of I-131 in sub

  13. Diagnostic Accuracy of Detecting Hashimoto's Thyroiditis in Thyroid Cancer Patients Who Underwent Thyroid Surgery: Comparison of Ultrasonography, Positron Emission Tomography/CT, Contrast Enhanced CT, and Anti-Thyroid Antibody

    International Nuclear Information System (INIS)

    To compare the diagnostic accuracy of ultrasonography (US), F18-fluorodeoxyglucose positron emission tomography/CT (PET/CT), contrast enhanced CT (CECT), serum anti-thyroid antibody for detecting Hashimoto's thyroiditis in thyroid cancer patients who underwent neck surgery. A total of 150 patients with suspicious for thyroid cancer, who had previously undergone US guided needle aspiration of thyroid, were evaluated with the use of US, PET/CT, CECT and serum anti-thyroid antibody. The four studies were performed within two months before neck surgery. Hashimoto's thyroiditis was confirmed by histopathological results. The diagnostic accuracy of US, PET/CT, CECT and serum anti-thyroid antibody were calculated statistically. Hashimoto's thyroiditis was diagnosed in 51 out of the 150 patients, following neck surgery. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of US were 76.5%, 92.9%, 84.8%, 88.5%, and 87.3%, respectively. The corresponding values of PET/CT were 37.3%, 96.0%, 82.6%, 74.8%, and 76.0%, and CECT were 62.7%, 89.9%, 76.2%, 82.4%, and 80.7%, and serum anti-thyroid antibody level were 90.2%, 93.9%, 88.5%, 94.9%, and 92.7%, respectively. McNemar test revealed significant difference among PET/CT and others, but no significant differences among US, CECT and serum anti-thyroid antibody. Overall, serum anti-thyroid antibody showed most accurate diagnostic performance. In detecting Hashimoto's thyroiditis, serum anti-thyroid antibody showed higher diagnostic accuracy than others. US also showed relatively high diagnostic accuracy.

  14. Association between Spontaneous abortion and Presence of anti thyroid antibodies in mother’s serum

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    Mahmoud Mirhosseini

    2012-12-01

    Results: Out of 51 subjects, 18 had positive Anti-TPO-Ab, of which -10 were among the cases and 8 belonged to the controls. Out of 18 women with positive AntiTG-Ab, 11 cases were in the control group and 7 were in the cases. The differences between the control group and the amounts of Anti-TPO-Abs (P=0.468 and Anti-TG-Abs (P=0.675 were not swignificant. Conclusion: The results revealed that there is no association between abortion and presence of antithyroid antibodies in mother’s serum. Other abortion causes such as various kinds of infections and smoking might be involved which requires more research.

  15. Anti-natrium/iodide symporter antibodies and other anti-thyroid antibodies in children with Turner's syndrome.

    Science.gov (United States)

    Kucharska, Anna M; Czarnocka, Barbara; Demkow, Urszula

    2013-01-01

    Antibodies against the Na/I symporter (anti-NIS ab) have been found in adult patients with autoimmune thyroid diseases. As easily available for the immune system, NIS can play a role in the initial stage of autoimmune thyroid diseases. Children with Turner's syndrome (TS) being at high risk of autoimmune thyroid disease development seem a valuable group for the investigation of the early autoimmune process. The aim of the study was to investigate the presence of anti-NIS ab and its potential clinical significance in TS children. Fifty four girls with TS were examined (age 11.9 ± 2.46 years), and 23 healthy girls with normal thyroid function, free of autoimmune diseases. Anti-NIS antibodies were measured by the in-house ELISA method and the Western blotting. Sera considered positive for anti-NIS ab were used for the iodide uptake bioassay using COS7 cells stably transfected with hNIS. In all patients the thyroid function, antithyroid antibodies presence and thyroid ultrasonography were evaluated. In 20% of the patients a subclinical hypothyroidism was diagnosed and 70.4% had antithyroid antibodies (anti-TPO - 64.8% and Anti-Tg - 24%). Anti-NISab were present in 14.8% girls with TS and in none of the control group. Their presence was unrelated to other antithyroid antibodies titre or patients' age. A positive correlation between the anti-NIS ab presence and the hypothyroidism was found (p < 0.04). Anti-NIS ab-positive sera did not suppress iodine uptake. In conclusion, anti-NIS antibodies were present in 14.8% of children with TS and they were related to the presence of hypothyroidism. PMID:22836628

  16. Effect of thione-thiol tautomerism on the inhibition of lactoperoxidase by anti-thyroid drugs and their analogues

    Indian Academy of Sciences (India)

    P N JAyaram; Gouriprasanna Roy; Govindasamy Mugesh

    2008-01-01

    The keto-enol type tautomerism in anti-thyroid drugs and their selenium analogues are described. The commonly used anti-thyroid drug methimazole exists predominantly in its thione form, whereas its selenium analogue exists in a zwitterionic form. To understand the effect of thione/thiol and selone/selenol tautomerism on the inhibition of peroxidase-catalysed reactions, we have synthesized some thiones and selones in which the formation of thiol/selenol forms are blocked by different substituents. These compounds were synthesized by a carbene route utilizing an imidazolium salt. The crystal structures of these compounds reveal that the C=Se bonds in the selones are more polarized than the C=S bonds in the corresponding thiones. The structures of selones were studied in solution by NMR spectroscopy and the 77Se NMR chemical shifts for the selones show large upfield shifts in the signals, confirming their zwitterionic structures in solution. The inhibition of lactoperoxidase by the synthetic thiones indicates that the presence of a free N-H moiety is essential for an efficient inhibition. In contrast, such moiety is not required for an inhibition by the selenium compounds.

  17. Determination of first trimester specific reference interval of anti thyroid peroxidase antibody - Study from a tertiary care hospital of Pakistan

    International Nuclear Information System (INIS)

    This study emphasizes the need of trimester specific reference interval of thyroid antibody while interpreting the results in pregnant women with a suspicion of sub-clinical autoimmune hypothyroidism. In this study we determine the first trimester specific reference interval of thyroid peroxidase antibody among clinically euthyroid pregnant women. We chosen the first trimester as early detection of autoimmune hypothyroidism during pregnancy is crucial to reduce the adverse pregnancy outcomes (miscarriages and preterm delivery), if treated appropriately. (author)

  18. Anti-thyroid drugs in pediatric Graves' disease.

    Science.gov (United States)

    John, Mathew; Sundrarajan, Rajasree; Gomadam, S Sridhar

    2015-01-01

    Graves' disease is the most common cause of hyperthyroidism in children. Most children and adolescents are treated with anti-thyroid drugs as the initial modality. Studies have used Methimazole, Carbimazole and Propylthiouracil (PTU) either as titration regimes or as block and replacement regimes. The various studies of anti-thyroid drug (ATD) treatment of Graves' disease in pediatric patients differ in terms of the regimes, remission rate, duration of therapy for adequate remission, follow up and adverse effects of ATD. Various studies show that lower thyroid hormone levels, prolonged duration of treatment, lower levels of TSH receptor antibodies, smaller goiter and increased age of child predicted higher chance of remission after ATD. A variable number of patients experience minor and major adverse effects limiting initial and long term treatment with ATD. The adverse effects of various ATD seem to more in children compared to that of adults. In view of liver injury including hepatocellular failure need of liver transplantation associated with PTU, the use has been restricted in children. The rate of persistent remission with ATD following discontinuation is about 30%. Radioactive iodine therapy is gaining more acceptance in older children with Graves's disease in view of the limitations of ATD. For individual patients, risk-benefit ratio of ATD should be weighed against benefits of radioactive iodine therapy and patient preferences. PMID:25932387

  19. Anti-thyroid drugs in pediatric Graves′ disease

    Directory of Open Access Journals (Sweden)

    Mathew John

    2015-01-01

    Full Text Available Graves′ disease is the most common cause of hyperthyroidism in children. Most children and adolescents are treated with anti-thyroid drugs as the initial modality. Studies have used Methimazole, Carbimazole and Propylthiouracil (PTU either as titration regimes or as block and replacement regimes. The various studies of anti-thyroid drug (ATD treatment of Graves′ disease in pediatric patients differ in terms of the regimes, remission rate, duration of therapy for adequate remission, follow up and adverse effects of ATD. Various studies show that lower thyroid hormone levels, prolonged duration of treatment, lower levels of TSH receptor antibodies, smaller goiter and increased age of child predicted higher chance of remission after ATD. A variable number of patients experience minor and major adverse effects limiting initial and long term treatment with ATD. The adverse effects of various ATD seem to more in children compared to that of adults. In view of liver injury including hepatocellular failure need of liver transplantation associated with PTU, the use has been restricted in children. The rate of persistent remission with ATD following discontinuation is about 30%. Radioactive iodine therapy is gaining more acceptance in older children with Graves′s disease in view of the limitations of ATD. For individual patients, risk-benefit ratio of ATD should be weighed against benefits of radioactive iodine therapy and patient preferences.

  20. Anti-thyroid drugs or 131I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis

    International Nuclear Information System (INIS)

    In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R$ 1,345.81, while the RAI group spent a mean amount of R$ 622.94. Therefore, the costs of the RAI treatment were 53.5% lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves' disease. (author)

  1. A novel enzyme-linked immunosorbent assay for quantitative detection of anti-thyroid peroxidase antibodies in serum%血清抗甲状腺过氧化物酶抗体ELISA定量方法的建立

    Institute of Scientific and Technical Information of China (English)

    孙颖; 李会强; 陈寅; 仁杰; 李婵

    2011-01-01

    Objective To establish a novel enzyme-linked immunosorbent assay (ELISA) for quantitative detection of the concentra tion of anti-thyroid peroxidase antibody (TPOAb) in serum. Methods The microtiter plate was coated with biotinylated bovine serum albumin (BSA) and streptavidin. The biotinylated TPO antigen and standardized anti-TPOAb or test sera were successively added into the wells of plate. The HRP-anti-IgG was then added into the plate for colorization. The optimal concentrations of biotinylated TPO an tigen and HRP-anti-IgG were screened by chessboard titration, and the reaction conditions were optimized for the method evaluation. Results In the indirect-coating mode, the amount of coated antigen was 0. 083 μg/mL. The sensitivity of the assay was 0. 165 IU/mL. The coefficient of variations (CV) of inter-assay in high and low concentration of serum mixture were 9.2% and 9.0% , and the CV of intra-assay were 4.6% and 5.6% respectively. The recovery rate was between 96% and 104%. The coated ELISA plate re mained stable for 5 days at 37 ℃. The rate of cross-reaction with anti-thyroid globulin (TGAb) was 0. 22%. The reference range in serum was less than 65. 7 IU/mL. The correlation coefficient of the experimental results with those of Abbott kit was 0. 985 (P < 0.01). Conclusion In the developed ELISA of indirect-coated mode, the amount of needed purified antigen significantly reduced. The sensitivity and specificity of the assay were satisfied. The method is simple and cost-saving, so it should be very suitable for anti TPOAb detection in primary hospitals.%目的 建立一种ELISA方法用于定量分析血清抗甲状腺过氧化物酶(TPO)抗体(TPOAb).方法 用生物素化牛血清清蛋白(BSA)和链霉亲合素包被微孔板,同时加入生物素化TPO抗原和待检血清,再加入酶标记抗人IgG,建立间接包被模式酶联免疫法测定抗TPO抗体.经方阵滴定确定生物素化抗原和酶标抗体的最适浓度,优化反应条件,

  2. Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne Mohawk young adults.

    Science.gov (United States)

    Schell, Lawrence M; Gallo, Mia V; Ravenscroft, Julia; DeCaprio, Anthony P

    2009-01-01

    Persistent organic pollutants, such as polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and p,p'-dichlorophenyldichloroethylene (DDE), have been found to elicit a broad spectrum of biologic, metabolic, and immunologic responses. The potential of these pollutants to impair immune responses and trigger autoimmune disease is of growing concern, given their structural similarity to thyroid hormones and their potential to modulate the mechanisms and interfere with the binding of these hormones. We examine the relationship of different groupings of PCBs, according to chlorination and structure, and of p,p'-DDE and HCB to anti-thyroid peroxidase antibody, a useful tool in the evaluation of thyroid dysfunction, among 115 young adults of the Akwesasne Mohawk Nation. Overall, 18 participants (15.4%) had anti-thyroid peroxidase antibodies (TPOAb) levels above the normal laboratory reference range (23% of females, 9% of males). Among participants who were breast fed (n=47), those with an elevated TPOAb level had significantly higher levels of all PCB groupings, with the exception of levels of non-persistent PCBs which did not differ significantly. Levels of p,p'-DDE were also significantly elevated, while HCB and mirex were not higher among those with elevated TPOAb. Also, after stratifying by breast-feeding status, participants who were breast fed showed significant, positive relationships between TPOAb levels and all PCB groupings, except groups comprised of non-persistent PCBs, and with p,p'-DDE, HCB, and mirex. No effects were evident among non-breast-fed young adults. Further studies are necessary to elucidate the site and mechanism of action of these persistent organic pollutants (POPs) and to establish thresholds for these effects, especially among populations with background levels of toxicant exposure. PMID:18995849

  3. Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne Mohawk young adults

    Science.gov (United States)

    Schell, Lawrence M.; Gallo, Mia V.; Ravenscroft, Julia; DeCaprio, Anthony P.

    2009-01-01

    Persistent organic pollutants, such as PCBs, HCB and DDE, have been found to elicit a broad spectrum of biologic, metabolic, and immunologic responses. The potential of these pollutants to impair immune responses and trigger autoimmune disease is of growing concern, given their structural similarity to thyroid hormones and their potential to modulate the mechanisms and interfere with the binding of these hormones. We examine the relationship of different groupings of PCBs, according to chlorination and structure, and of p,p’-DDE and HCB to anti-thyroid peroxidase antibody, a useful tool in the evaluation of thyroid dysfunction, among 115 young adults of the Akwesasne Mohawk Nation. Overall, eighteen participants (15.4%) had TPOAb levels above the normal laboratory reference range (23% of females, 9% of males). Among participants who were breast fed (n=47), those with an elevated TPOAb level had significantly higher levels of all PCB groupings, with the exception of levels of non-persistent PCBs which did not differ significantly. Levels of p,p’-DDE were also significantly elevated, while HCB and mirex were not higher among those with elevated TPOAb. Also, after stratifying by breast feeding status, participants who were breast fed showed significant, positive relationships between TPOAb levels and all PCB groupings, except groups comprised of non-persistent PCBs, and with p,p’-DDE, HCB, and mirex. No effects were evident among non-breastfed young adults. Further studies are necessary to elucidate the site and mechanism of action of these POPs and to establish thresholds for these effects, especially among populations with background levels of toxicant exposure. PMID:18995849

  4. Outcome of graves' disease after anti-thyroid drug treatment in South West of Iran

    International Nuclear Information System (INIS)

    Objective: This study was conducted to observe the optimal results of long term treatment with antithyroid drugs in patients with graves' disease. Methodology: Total of 268 patients with graves' disease who were referred to endocrinology clinic during 2005 - 2008 and treated with anti-thyroid drugs for a long term were studied. Data about the age, gender, estimated weight of thyroid before and after the treatment, level of thyroid hormones, disease relapse, hypothyroidism and the drug side-effects were collected and analyzed. Results: Eighty two (31%) patients were males, 186 (69%) females, mean age of 35 +- 27 years and follow-up course of 31+- 16 months], were studied. After the discontinuation of long term treatment, 53% were affected with relapse of hyperthyroidism. The mean duration of hyperthyroidism relapse after the treatment was 8.3 +- 7.3 months. The relapse rate was and patients with large thyroid and lower TSH level at the end of treatment, the rate of relapse treatment was about 6%. More decrease of thyroid size during the treatment course, higher level of serum TSH after discontinuation of the treatment, and lower thyroid hormone levels before the treatment were some of the effective factors in hypothyroidism incidence (P=0.005, patients (39%) remained euthyroid in the follow-up course. Conclusion: patients with graves' especially in middle-aged women with smaller goiters. (author)

  5. Functional effects of anticardiolipin antibodies.

    Science.gov (United States)

    Harris, E N; Pierangeli, S S

    1996-10-01

    The 'lupus anticoagulant' phenomenon is the best documented functional effect of antiphospholipid (aPL) antibodies, occurring either by inhibition of the prothrombinase and/or Factor X activation reactions. Understanding the mechanism by which aPL antibodies inhibit phospholipid dependent coagulation reactions may yield important clues about their 'thrombogenic effects' in vivo. We conducted a series of studies to determine the specificity, diversity, and mechanism by which aPL antibodies inhibit phospholipid dependent reactions. Results showed that purified immunoglobulins with lupus anticoagulant and anti-cardiolipin activities were absorbed by negatively charged phospholipids and both activities were recovered from the phospholipid-antibody precipitate. Purified aPL antibodies inhibited the prothrombinase reaction in a plasma free system in which beta 2-glycoprotein 1 (beta 2-GP1) was absent. Affinity purified aPL antibodies had 25-50 times the inhibitory activity of immunoglobulin preparations. The phospholipid binding proteins, beta 2-GPI and placental anticoagulant protein I (PAP I), independently inhibited the prothrombinase reaction, and when these proteins were combined with aPL, inhibition of the prothrombinase reaction was additive. Antibodies of syphilis had no inhibitory effect, partially accounted for by lack of specificity for phosphotidylserine (PS). Although aPL antibodies inhibited the protein C activation reaction, there was no correlation of these activities with inhibition of the prothrombinase reaction. Together, these results show that aPL exert their effects by interaction with negatively charged phospholipids, in particular phosphotidylserine, but lack of correlation between inhibition of the prothrombinase and protein C activation reactions, suggests that the nature of the coagulation protein is also important. PMID:8902763

  6. Mechanism for the anti-thyroid action of minocycline

    Energy Technology Data Exchange (ETDEWEB)

    Doerge, D.R.; Divi, R.L.; Deck, J. [National Center for Toxicological Research, Jefferson, AR (United States); Taurog, A. [Univ. of Texas, Dallas, TX (United States)

    1997-01-01

    Administration of minocycline (MN), a tetracycline antibiotic, produces a black pigment in the thyroids of humans and several species of experimental animals and antithyroid effects in rodents. We have previously shown that these effects appear to be related to interactions of MN with thyroid peroxidase (TPO), the key enzyme in thyroid hormone synthesis. In the present study, the mechanisms for inhibition of TPO-catalyzed iodination and coupling reactions by MN were investigated. 37 refs., 7 figs., 3 tabs.

  7. Production, isolation, and characterization of rabbit anti-idiotypic antibodies directed against human antithyrotrophin receptor antibodies.

    OpenAIRE

    Baker, J. R.; Lukes, Y G; Burman, K. D.

    1984-01-01

    Previous studies have shown that anti-idiotypic antibodies can be developed in vivo through animal immunization with idiotype, and that these antibodies can be isolated from other anti-immunoglobulin antibodies by affinity purification. These techniques have relied on large amounts of idiotype, which were produced either by hyperimmunization or by monoclonal antibodies, to serve as the affinity adsorbent. In the present study, we produced anti-idiotypic antibodies to human anti-thyroid-stimul...

  8. Thyroid hormone synthesis and anti-thyroid drugs: A bioinorganic chemistry approach

    Indian Academy of Sciences (India)

    Gouriprasanna Roy; G Mugesh

    2006-11-01

    Hydrogen peroxide, generated by thyroid oxidase enzymes, is a crucial substrate for the thyroid peroxidase (TPO)-catalysed biosynthesis of thyroid hormones, thyroxine (T4) and triiodothyronine (T3) in the thyroid gland. It is believed that the H2O2 generation is a limiting step in thyroid hormone synthesis. Therefore, the control of hydrogen peroxide concentration is one of the possible mechanisms for the inhibition of thyroid hormone biosynthesis. The inhibition of thyroid hormone synthesis is required for the treatment of hyperthyroidism and this can be achieved by one or more anti-thyroid drugs. The most widely used anti-thyroid drug methimazole (MMI) inhibits the production of thyroid hormones by irreversibly inactivating the enzyme TPO. Our studies show that the replacement of sulphur in MMI by selenium leads to a selone, which exists predominantly in its zwitterionic form. In contrast to the sulphur drug, the selenium analogue (MSeI) reversibly inhibits the peroxidase-catalysed oxidation and iodination reactions. Theoretical studies on MSeI reveal that the selenium atom in this compound carries a large negative charge. The carbon-selenium bond length in MSeI is found to be close to single-bond length. As the selenium atom exhibits a large nucleophilic character, the selenium analogue of MMI may scavenge the hydrogen peroxide present in the thyroid cells, which may lead to a reversible inhibition of thyroid hormone biosynthesis.

  9. Establishment of a Radioimmunoassay for Anti-thyroid Peroxidase Antibodies in Human Serum

    Institute of Scientific and Technical Information of China (English)

    YANQiang-fen; ZHANGLi-ling; GUOZhen

    2003-01-01

    Quantitative assay for circulating TPOAb is the most sensitive test for autoimmune thyroid diseases.It is also used in assessing long-term risk of thyroid dysfunction in postmenopausal women and plays an important role in managing pregnancy and postpartum thyroiditis.

  10. The prevalence of anti-thyroid peroxidase antibodies in subclinical and clinical hypothyroid patients

    Directory of Open Access Journals (Sweden)

    Jayashankar C.A.

    2015-12-01

    Results: Out of 50 cases, 28 subjects had clinical hypothyroidism (25 females and 3 males and 22 had subclinical hypothyroidism (14 females and 8males. Among the 50 subjects with clinical and subclinical hypothyroidism, 33 were anti-TPO positive. The corresponding percentage of anti-TPO positivity noted in the clinical hypothyroidism and subclinical hypothyroidism groups were 80 % and 50% respectively. Conclusions: Serum TSH and anti-TPO analyses are essential in determining the etiology of hypothyroidism and risk of progression to overt hypothyroidism in patients with subclinical. [Int J Res Med Sci 2015; 3(12.000: 3564-3566

  11. New antibacterial, non-genotoxic materials, derived from the functionalization of the anti-thyroid drug methimazole with silver ions.

    Science.gov (United States)

    Sainis, I; Banti, C N; Owczarzak, A M; Kyros, L; Kourkoumelis, N; Kubicki, M; Hadjikakou, S K

    2016-07-01

    The new silver(I) compound {[AgBr(μ2-S-MMI)(TPP))]2} (1) and the known one [AgCl(TPP)2(MMI)] (2) were obtained by refluxing toluene solutions of silver(I) halide with triphenylphosphine (TPP) and the anti-thyroid drug 2-mercapto-1-methyl-imidazole or methimazole (MMI). The complexes were characterized by m.p., vibrational spectroscopy (mid-FT-IR), (1)H, (31)P-NMR, UV-Vis spectroscopic techniques and X-ray crystallography. The antibacterial effect of 1 and 2 against the bacterial species Pseudomonas aeruginosa (PAO) and Escherichia coli was evaluated. Compound 1 exhibits comparable activity to the corresponding one of the silver nitrate which is an antibacterial drug in use. The in vivo genotoxicity of 1-2 by the mean of Allium cepa test shows no alterations in the mitotic index values due to the absence of chromosomal aberrations. The mechanism of action of the title compounds is evaluated. The DNA binding tests indicate the ability of the complexes 1-2 to modify the activity of the bacteria. The binding constants of 1-2 towards CT-DNA indicate interaction through opening of the hydrogen bonds of DNA. Docking studies on DNA-complexes interactions confirm the binding of both complexes 1-2 in the major groove of the CT-DNA. In conclusion the silver complex 1 is an anti-bacterial and non-genotoxic material, which can be applied to antibacterial drug in the future. PMID:26765999

  12. Thyroid uptake of I-131 during anti-thyroid drug treatment

    International Nuclear Information System (INIS)

    Hyperthyroidism is a global ailment and its treatment is very promising either by ant-thyroid drug or by radioiodine. Iodine-131 uptake test is very important for evaluation of hyperthyroid in respect to its therapy and to exclude thyroiditis. This study was performed to observe the thyroid uptake pattern during intake of anti-thyroid medicine and workout the possibility to start I-131 therapy just after withdraw of antithyroid drug without waiting few days. In this study total 252 patient's I-131 uptake test is performed. Among the patient 135 (53.57%) were female, 117 (64.43%) were male. All this patients were hyperthyroid both clinically and biochemically. Thyroid uptake was taken to all patients at 24 hours after oral administration of 5 to 10 micro-curie of I -131. Uptake was taken by an uptake system and recorded as percentage uptake. These patients are grouped into three categories. Group-A-newly diagnosed cases, who have not taken antithyroid drug or I-131 therapy, there were 82 patients in this group, and their mean uptake was 37.12 ±18.5%. Group B - this group of patients were studied during intake of antithyroid medicine, there were 130 patients in this group and their mean uptake was 34.34±16.0%. Group-B patients were further divided in two sub-groups, patients having antithyroid drug for 1 to 3 weeks (group-B 1), group B1 have mean uptake 37±21% and those were taking antithyroid for 3 weeks to 2 years (group-B2), group B2 have uptake 34.34±20%. Group C- these patients are taken from those patients who had withdrawn antithyroid drug for 3 days to 3 months, there were 40 such patients. Group C further divided into two sub-group, group-C1 (stopped for 3-10 days) and group C2 (stopped for 11 days to 3 months). Group C1 had mean uptake 38±16% and group C2 had mean uptake 35±19%. From this study it is observed that Iodine-131 uptake percentage of untreated hyperthyroid; during antithyroid drug treatment and after withdraw of antithyroid drug almost

  13. G raves’ disease – anti-thyroid autoantibodies and function thyroid status

    International Nuclear Information System (INIS)

    Full text: Introduction: Hyperthyroidism is an autoimmune disease in the pathogenesis of which a key role play the antibodies against the thyroid stimulating hormone receptor (TRAb). The aim of this study is to analyze the immune and hormonal status in patients with Graves' disease, who are on thyreostatic therapy and in remission. Materials and methods: 67 patients were studied - 11 men and 56 women - with Graves' disease, mean age 49.7 years (range - 20-76 ). Of these, 55 were on thyreostatic therapy (two subgroups: 27 - treated up to 24 months , and 28 with relapsed disease ) and 12 were in remission up to a year. Patient's condition is assessed as a complex of clinical, biochemical, including hormonal, immune status and ultrasonography of the thyroid gland. We examined thyroid stimulating hormone, free thyroxine, free triiodothyronine, antityreoperoxidase antibodies (Anti-TPO) and TRAb. The patients on therapy are: in hyperthyroidism - 10/ 14 with subclinical hyperthyroidism - 9/8, euthyroid - 7/6 and with subclinical hypothyroidism - 1/0. Results: The patients with hyperthyroidism ( 43.6% ) in both thyreostatic therapy groups have a significantly higher average values of TRAb. The patients with subclinical hyperthyroidism and relapse showed higher levels of TRAb in comparison with those undergoing therapy to 24 months after diagnosing. The values of TRAb in the euthyroid patients in both groups of treatment were 1,5 IU / l. The Anti-TPO values were increased in 78.2% of the patients on therapy and 55.5% of those in remission. Conclusion: With the decrease of thyroid hormones during treatment of Hyperthyroidism the levels of TRAb and Anti-TPO decrease. The TRAb values are useful for the monitoring the effect of the thyreostatic treatment, determining the therapeutic approach in patients with a sustained reduction of TRAb in the course thyreostatic therapy and particularly for relapse

  14. Antibody

    Science.gov (United States)

    An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples ... microorganisms (bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produced when the immune system mistakenly ...

  15. Anti-thyroid drugs or {sup 131}I therapy to control the hyperthyroidism of graves disease: a cost-effectiveness analysis; Tratamento clinico com drogas antitireoidianas ou dose terapeutica de Iodo-131 no controle do hipertireoidismo na doenca de Graves: avaliacao dos custos e beneficios

    Energy Technology Data Exchange (ETDEWEB)

    Cruz Junior, Antonio Fiel; Takahashi, Miriam Hideco; Albino, Claudio Cordeiro [Universidade Estadual de Londrina, PR (Brazil)]. E-mail: afiel@bs2.com.br

    2006-12-15

    In this study, we set out to evaluate the costs and effectiveness of the 2 most used therapies in our region, ATD or RAI. 23 patients, 6 men and 16 women, with a mean age of 35.4 years, treated with ATD, and 35 patients, 5 men and 30 women, mean age of 39.4 years, treated with RAI, were studied. After 2 years receiving ATD, 21 patients achieved euthyroidism and 2 remained hyperthyroid. In the RAI group, 21 patients presented hypothyroidism and 13 became euthyroid. To calculate the costs of each therapy, we analyzed the number of visits during this period, the laboratory data and the drugs needed, such as tiamazol and/or thyroxine. The group treated only with ATD needed a higher number of visits and laboratory measurements, with the mean total cost of R$ 1,345.81, while the RAI group spent a mean amount of R$ 622.94. Therefore, the costs of the RAI treatment were 53.5% lower than clinical therapy with ATD. The present study demonstrates that RAI treatment has a lower cost than ATD, being very effective in controlling the hyperthyroidism of Graves' disease. (author)

  16. A Case of Marine-Lenhart Syndrome with a Negative TSH Receptor Antibody Titer Successfully Treated with a Fixed, Low Dose of I131

    OpenAIRE

    Masahiro Takei; Hiroaki Ishii; Yoshihiko Sato; Mitsuhisa Komatsu

    2014-01-01

    We herein describe a case of Marine-Lenhart syndrome with a negative TSH receptor antibody titer. A 75-year-old female presented to our hospital with malaise, palpitations, and mild fine tremors. She did not have any signs suggestive of Graves' ophthalmopathy, including conjunctival injection, periorbital edema, or proptosis. Her laboratory data were negative for thyroid autoantibodies, including anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and anti-TSH receptor antibodi...

  17. Side-effects of monoclonal antibodies during immunoscintigraphy

    International Nuclear Information System (INIS)

    When monoclonal antibodies, most of which are developed from mouse hybridomas, are injected into the patient they are recognized as foreign globulins. The resulting immune response leads to the development of human anti-mouse antibodies or so called side-effects. (author). 1 ref

  18. Production, isolation, and characterization of rabbit anti-idiotypic antibodies directed against human antithyrotrophin receptor antibodies.

    Science.gov (United States)

    Baker, J R; Lukes, Y G; Burman, K D

    1984-01-01

    Previous studies have shown that anti-idiotypic antibodies can be developed in vivo through animal immunization with idiotype, and that these antibodies can be isolated from other anti-immunoglobulin antibodies by affinity purification. These techniques have relied on large amounts of idiotype, which were produced either by hyperimmunization or by monoclonal antibodies, to serve as the affinity adsorbent. In the present study, we produced anti-idiotypic antibodies to human anti-thyroid-stimulating hormone (TSH) receptor antibodies by first injecting rabbits with (TSH receptor purified) IgG from Graves' patients. The resulting antiserum was then adsorbed with Sepharose-coupled TSH in an attempt to specifically bind and isolate the anti-idiotype. The antibody obtained from this process was shown to bind specifically to TSH receptor-binding antibodies from Graves' patients, and this binding could be inhibited by 56% with the addition of 10(-4) M TSH but not by HCG (10(-2) M). The anti-idiotype also bound to TSH, and this binding could be specifically inhibited by receptor-purified Graves' IgG (60% inhibition at 10 micrograms/ml IgG), but not by IgG from normal subjects (no inhibition at 50 micrograms/ml IgG). In a TSH receptor binding assay, the anti-idiotype could inhibit TSH receptor binding in Graves' sera at a 1,000-fold lower concentration than could anti-kappa/lambda antiserum; the anti-idiotypic antiserum also inhibited in vitro TSH-mediated adenylate cyclase stimulation at an IgG concentration of 5 micrograms/ml, while heterologous anti-TSH antisera and normal IgG at similar concentrations had no effect. Finally, despite being generated against a single patient's TSH receptor binding antibody, the anti-idiotype was able to block TSH receptor binding in the serum of six other Graves' patients, thus suggesting that there may be conformational conservation in the antigen that is recognized by different individuals' TSH receptor-binding immunoglobulins. PMID

  19. Sertraline and its iodine product: Experimental and theoretical vibrational studies. Potential in vitro anti-thyroid activity of sertraline and iodine product toxicity with respect to male Wistar rats

    Science.gov (United States)

    Escudero, Graciela E.; Ferraresi Curotto, Verónica; Laino, Carlos H.; Pis Diez, Reinaldo; Williams, Patricia A. M.; Ferrer, Evelina G.

    2013-03-01

    Mayor depression, obsessive-compulsive panic, social anxiety disorders are common diseases that are usually treated with sertraline hydrochloride which is the active ingredient of the well known drugs as Zoloft and Lustral. In this work, we presented a more complete vibrational characterization of the solid phase FT-IR spectra of Sertraline hydrochloride and its sertraline-iodine product in which the conformational space of the molecules was investigated performing molecular dynamic simulations within an NVT ensemble. Geometrical, electronic and vibrational properties were calculated with the density functional theory. Comparison of the simulated spectra with the experimental spectra provides important information about the ability of the computational method to describe the vibrational modes of both molecules. In addition, for the first time we present the evaluation of anti-thyroid activity of sertraline hydrochloride by using the Lang's method. Also, with the aim to evaluate the antidepressant effect of its iodine product we demonstrated for this compound the toxic effect towards the male Wistar rats.

  20. Lung injury mediated by antibodies to endothelium. II. Study of the effect of repeated antigen-antibody interactions in rabbits tolerant to heterologous antibody.

    OpenAIRE

    Camussi, G.; Caldwell, P. R.; Andres, G.; Brentjens, J. R.

    1987-01-01

    The effect of repeated interactions of antibodies with cell surface antigens have been examined in in vitro, but not in in vivo systems. In this study are described the results of multiple antibody-cell surface antigen interactions in vivo. Rabbits were given repeated intravenous injections of goat antibodies to angiotensin converting enzyme (ACE), an antigen expressed on the surface of lung endothelial cells. For prevention of anaphylactic reactions, which would have been induced by multiple...

  1. Comparisons of the effect of naturally acquired maternal pertussis antibodies and antenatal vaccination induced maternal tetanus antibodies on infant's antibody secreting lymphocyte responses and circulating plasma antibody levels.

    Science.gov (United States)

    Ahmad, Shaikh Meshbahuddin; Alam, Jahangir; Afsar, Nure Alam; Huda, Nazmul; Kabir, Yearul; Qadri, Firdausi; Raqib, Rubhana; Stephensen, Charles B

    2016-04-01

    The goal of this study was to explore the effects of trans-placental tetanus toxoid (TT) and pertussis (PT) antibodies on an infant's response to vaccination in the context of antenatal immunization with tetanus but not with pertussis. 38 mothers received a single dose of TT vaccine during pregnancy. Infants received tetanus and pertussis vaccines at 6, 10 and 14 wk of age. TT and PT anti-IgG secretion by infant lymphocytes was measured at 15 wk. Plasma antibodies were measured at 6 wk (pre-vaccination), 15 wk and 1 y of age. Prior to vaccination, TT and PT antibody were detected in 94.6% and 15.2% of infants. At 15 wk anti-TT-IgG and anti-PT-IgG in plasma was increased by 7-9 fold over pre-vaccination levels, while at 1 y plasma anti-TT-IgG was decreased by approximately 5-fold from the peak and had returned to near the pre-vaccination level. At 1 y plasma anti-PT-IgG was decreased by 2-fold 1 yfrom the 15 wk level. However, 89.5% and 82.3% of infants at 1 y had protective levels of anti-TT and anti-PT IgG, respectively. Pre-vaccination plasma IgG levels were associated with lower vaccine-specific IgG secretion by infant lymphocytes at 15 wk (p < 0.10). This apparent inhibition was seen for anti-TT-IgG at both 15 wk (p < 0.05) and t 1 y (p < 0.10) of age. In summary, we report an apparent inhibitory effect of passively derived maternal antibody on an infants' own antibody response to the same vaccine. However, since the cut-off values for protective titers are low, infants had protective antibody levels throughout infancy. PMID:27176823

  2. A Case of Marine-Lenhart Syndrome with a Negative TSH Receptor Antibody Titer Successfully Treated with a Fixed, Low Dose of I131

    Directory of Open Access Journals (Sweden)

    Masahiro Takei

    2014-01-01

    Full Text Available We herein describe a case of Marine-Lenhart syndrome with a negative TSH receptor antibody titer. A 75-year-old female presented to our hospital with malaise, palpitations, and mild fine tremors. She did not have any signs suggestive of Graves’ ophthalmopathy, including conjunctival injection, periorbital edema, or proptosis. Her laboratory data were negative for thyroid autoantibodies, including anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and anti-TSH receptor antibodies (TRAb. Ultrasonography of the thyroid gland revealed a tumor in the right lobe. The remaining thyroid gland had an inhomogeneous and rough texture with a high color Doppler flow. I123 scintigraphy disclosed a hot nodule in the right thyroid gland corresponding to the tumor detected on ultrasonography, suggesting Plummer disease. Furthermore, there was an increased uptake of radionuclide in the rest of the thyroid gland, despite the suppressed level of TSH and negative titer of TRAb, suggesting underlying Graves’ disease. The present findings suggested a diagnosis of Marine-Lenhart syndrome with a negative TRAb titer. Treatment with 10 mCi of radioiodine was highly effective in treating hyperthyroidism in this case. A negative TSH receptor antibody titer does not necessarily rule out the existence of Graves’ disease in patients with Plummer disease.

  3. ANTITUMOR EFFECTS OF MONOCLONAL ANTIBODY FAB′ FRAGMENT CONTAINING IMMUNOCONJUGATES

    Institute of Scientific and Technical Information of China (English)

    刘小云; 甄永苏

    2002-01-01

    Objective.Using monoclonal antibody (mAb) Fab′ fragment to develop mAb immunoconjugates for cancer. Methods.Fab′ fragment of mAb 3A5 was prepared by digestion of the antibody with pepsin and then reduced by dithiothreitol (DTT),while Fab′ fragment of mAb 3D6 was obtained by digestion of the antibody with ficin and subsequently reduced by β mercaptoethanol.The conjugation between Fab′ fragment and pingyangmycin (PYM),an antitumor antibiotic,was mediated by dextran T 40.Immunoreactivity of Fab′ PYM conjugates with cancer cells was determined by ELISA,and the cytotoxicity of those conjugates to cancer cells was determined by clonogenic assay.Antitumor effects of the Fab′ PYM conjugates were evaluated by subcutaneously transplanted tumors in mice. Results.The molecular weight of Fab′ fragment was approximately 53 kD,while the average molecular weight of Fab′ PYM conjugate was 170 kD.The Fab′ PYM conjugates showed immunoreactivity with antigen relevant cancer cells and selective cytotoxicity against target cells.Administered intravenously,Fab′ PYM conjugates were more effective against the growth of tumors in mice than free PYM and PYM conjugated with intact mAb. Conclusion.Fab′ PYM conjugate may be capable of targeting cancer cells and effectively inhibiting tumor growth,suggesting its therapeutic potential in cancer treatment.

  4. Combination effect on HIV infection in vitro of soluble CD4 and HIV-neutralizing antibodies

    DEFF Research Database (Denmark)

    Hansen, J E; Sørensen, A M; Olofsson, S; Osinaga, E; Roseto, A

    In combination with HIV gp120 V3-loop antibody, two carbohydrate specific neutralizing antibodies (83D4 and 2G12) had a synergistic neutralizing effect on HIV infection. However, sCD4 and an antibody which blocks gp 120/CD4 binding (1B1) both displayed antagonism.......In combination with HIV gp120 V3-loop antibody, two carbohydrate specific neutralizing antibodies (83D4 and 2G12) had a synergistic neutralizing effect on HIV infection. However, sCD4 and an antibody which blocks gp 120/CD4 binding (1B1) both displayed antagonism....

  5. Autoimmune thyroiditis in antinuclear antibody positive children without rheumatologic disease

    Directory of Open Access Journals (Sweden)

    Arkachaisri Thaschawee

    2010-05-01

    Full Text Available Abstract Background Children are commonly referred to a pediatric rheumatology center for the laboratory finding of an Anti-nuclear antibody (ANA of undetermined significance. Previous studies regarding adult rheumatology patients have supported an association between ANA and anti-thyroid antibodies, with the prevalence of thyroid antibodies being significantly higher in patients referred to a rheumatology center for an ANA without evidence of connective tissue disease compared to the general population. The purpose of the present study was to determine the frequency of thyroid antibodies in children referred to a pediatric rheumatology center for a positive ANA without evidence of a connective tissue disease. Methods A retrospective chart review was performed on children who were referred to our pediatric rheumatology center between August 2003 and March 2007 for positive ANA with concurrent thyroid antibody and thyroid function tests performed who did not fulfill criteria for a specific connective tissue disease. Laboratory and clinical features were recorded and analyzed. Mean and standard deviation were used to describe continuous data. Chi-square or Fisher's exact tests were used to compare proportions between variables. Results One-hundred and four ANA-positive patients with concurrent thyroid studies were evaluated (88% female, 93% Caucasian, mean age 11.9 ± 4.0 years. Half of patients had an ANA titer ≥ 1:320. The ANA pattern was speckled in 60% of the patients. Thyroid antibodies were detected in 30% of the patients. Anti-Thyroglobulin (ATG was detected in 29% and Anti-thyroid peroxidase (ATPO in 21% of the patients; of these children, 14% had hypothyroidism. ANA pattern and titer were not associated with anti-thyroid antibody positivity. Conclusion Thyroid antibodies associated with chronic lymphocytic thyroiditis, ATG and ATPO, were detected significantly higher in ANA-positive children without a rheumatologic condition (30% as

  6. Effect of an anti-thyroid drug, 2,8-Dimercapto-6-hydroxy purine on reproduction in male rats.

    Science.gov (United States)

    Jahan, Sarwat; Ahmed, Shakeel; Emanuel, Erum; Fatima, Ismat; Ahmed, Hussain

    2012-04-01

    This histomorphological study is designed to evaluate the peripheral action of 2,8-Dimercapto-6-hydroxypurine (an antithyroid drug) on male reproductive system. The drug was administered as i.p. injection for 21 days to investigate its role on morphology of intratesticular cells and plasma testosterone level. Adult male rats (n=12), divided into three groups i.e. control, dimethylsulphoxide (DMSO) and 2,8-Dimercapto-6-hydroxypurine treated groups and treated with saline, DMSO and 2,8-Dimercapto-6-hydroxypurine for 21 consecutive days respectively. Blood samples were collected at day 1, 7, 14 and 21 and analyzed by using EIA systems. All the animals were scarified on 22nd day and testicular tissues were studied by histomorphpological assesment. 2,8-Dimercapto-6-hydroxypurine caused a significant decrease (P<0.0001) in mean testicular cell population, testicular cell diameter and resulted in arrested spermatogenesis. A significant decrease (P<0.0001) was observed in mean Sertoli and Leydig cell population and diameter in treated group. Similarly a significant decrease was observed in plasma testosterone levels at days 1, 7 and 14 (P<0.05) and further decrease by day 21 (P<0.01) of drug treatment. The present study suggests that 2,8-Dimercapto-6-hydroxypurine is a negative modulator of reproductive system as it suppressed the plasma testosterone level and proliferation of different testicular cell types in adult male rats. PMID:22459469

  7. How does fatty acid influence anti-thyroid drugs binding and specificity toward protein human serum albumin? A blind docking simulation study

    Indian Academy of Sciences (India)

    Bijan K Paul; Nikhil Guchhait

    2014-11-01

    This study reports an AutoDock-based blind docking simulation investigation to characterize the binding interaction of a series of anti-thyroid drugs (2-mercapto-1-methylimidazole (MMI), 2-thiouracil (TU), 6-methyl-2-thiouracil (MTU), 6--propyl-2-thiouracil (PTU) with a model plasma protein Human SerumAlbumin (HSA) in the presence and absence of fatty acid (FA). The drug-protein binding efficiency is characterized in terms of binding free energy and the association constant (Ka, which is estimated as the reciprocal of the inhibition constant, Ki) of the drugs to the transport protein. The study also unveils the substantial impact of the presence of fatty acid (FA) on the binding interaction process. It is shown that in the presence of FA the drug-protein binding efficiency is markedly enhanced (except for MTU) and the binding location is changed. Hydrogen bonding interaction appears to play a governing role in the process of FA-induced modifications of binding efficiency and location.

  8. Effects of deceleration on the humoral antibody response in rats

    Science.gov (United States)

    Barone, R. P.; Caren, L. D.; Oyama, J.

    1985-01-01

    Effects of hypergravity, simulated by chronic centrifugation, followed by a return to normal G (deceleration) on the immune system of rats were investigated. Two groups of male rats (28 days at 2.1 G, and 3.1 G) were compared to the control group (1.0 G). The animals were immunized by i.p. injections of sheep red blood cells on days 29, 42, and 57, and bled on days 36, 47, and 62. While the centrifuged rats ate and gainedsignificantly less than the control rats, the antibody titers and the organ/body mass ratios for the adrenal glands, kidneys, lungs, heart, and thymus were unaffected by gravity exposures, as were the values of the hematocrit and the white blood cell counts. It is concluded that deceleration does not adversely affect these particular aspects of the immune system.

  9. Gamma radiations an effective way of monoclonal antibodies sterilization

    International Nuclear Information System (INIS)

    The sterilization for radiations of pharmaceutical products is an effective, sure and reliable procedure; that it have been proving technically and grateful for different pharmacopoeia. The Monoclonal Antibodies (Acm) produced in the Center of Molecular Immunology (CIM) are products parenteral for the one which results indispensable that they complete the requirements of established sterility. The radio sterilization result the method more recommend for the sterilization of the Acm deep drying, due to the contained first floor of humidity remnant that minimizes the formation of sub-product that they affect their properties. With the objective of proposing a good dose of irradiation for the sterilization, we were carried out a study of the radius sensibility so much of the product like of the polluting of greater frequency of isolation of the clean area of the CIM. The characterization of the radius sensibility of the different micro- organisms was determined by D10 characteristic of each isolated strains. From the developed studies the Gram-positive rods endospore-forming were the most resistant strains at the deep drying, the radiations and they were of the greater frequency of apparition in the carried out isolations. We could conclude that utilizing a dose of 10 kGy it is possible to eliminate of the pollution more radio resistant, assuring the sterility required in the product, and without inducing effects under desire radiolytic in the same

  10. Local immunotherapy based on agonistic CD40 antibodies effectively inhibits experimental bladder cancer

    OpenAIRE

    Sandin, Linda C; Tötterman, Thomas H; Sara M. Mangsbo

    2014-01-01

    Local immunotherapy resurfaces in the field of cancer as a potential way to cure localized and metastatic disease with limited toxic effects. We have recently demonstrated that local administration of agonistic CD40 antibodies can cure localized as well as disseminated bladder neoplasms. This approach reduces the circulating concentrations of antibodies that would result from systemic delivery, hence resulting in limited toxicity.

  11. Effects of tau domain-specific antibodies and intravenous immunoglobulin on tau aggregation and aggregate degradation.

    Science.gov (United States)

    Esteves-Villanueva, Jose O; Trzeciakiewicz, Hanna; Loeffler, David A; Martić, Sanela

    2015-01-20

    Tau pathology, including neurofibrillary tangles, develops in Alzheimer's disease (AD). The aggregation and hyperphosphorylation of tau are potential therapeutic targets for AD. Administration of anti-tau antibodies reduces tau pathology in transgenic "tauopathy" mice; however, the optimal tau epitopes and conformations to target are unclear. Also unknown is whether intravenous immunoglobulin (IVIG) products, currently being evaluated in AD trials, exert effects on pathological tau. This study examined the effects of anti-tau antibodies targeting different tau epitopes and the IVIG Gammagard on tau aggregation and preformed tau aggregates. Tau aggregation was assessed by transmission electron microscopy and fluorescence spectroscopy, and the binding affinity of the anti-tau antibodies for tau was evaluated by enzyme-linked immunosorbent assays. Antibodies used were anti-tau 1-150 ("D-8"), anti-tau 259-266 ("Paired-262"), anti-tau 341-360 ("A-10"), and anti-tau 404-441 ("Tau-46"), which bind to tau's N-terminus, microtubule binding domain (MBD) repeat sequences R1 and R4, and the C-terminus, respectively. The antibodies Paired-262 and A-10, but not D-8 and Tau-46, reduced tau fibrillization and degraded preformed tau aggregates, whereas the IVIG reduced tau aggregation but did not alter preformed aggregates. The binding affinities of the antibodies for the epitope for which they were specific did not appear to be related to their effects on tau aggregation. These results confirm that antibody binding to tau's MBD repeat sequences may inhibit tau aggregation and indicate that such antibodies may also degrade preformed tau aggregates. In the presence of anti-tau antibodies, the resulting tau morphologies were antigen-dependent. The results also suggested the possibility of different pathways regulating antibody-mediated inhibition of tau aggregation and antibody-mediated degradation of preformed tau aggregates. PMID:25545358

  12. Effect of kinase inhibitors on the therapeutic properties of monoclonal antibodies

    OpenAIRE

    Duong, Minh Ngoc; Matera, Eva-Laure; Mathé, Doriane; Evesque, Anne; Valsesia-Wittmann, Sandrine; Clémenceau, Béatrice; Dumontet, Charles

    2014-01-01

    Targeted therapies of malignancies currently consist of therapeutic monoclonal antibodies and small molecule kinase inhibitors. The combination of these novel agents raises the issue of potential antagonisms. We evaluated the potential effect of 4 kinase inhibitors, including the Bruton tyrosine kinase inhibitor ibrutinib, and 3 PI3K inhibitors idelalisib, NVP-BEZ235 and LY294002, on the effects of the 3 monoclonal antibodies, rituximab and obinutuzumab (directed against CD20) and trastuzumab...

  13. Mycofix ameliorative effect on Newcastle disease antibody production in broiler chickens during aflatoxicosis

    Directory of Open Access Journals (Sweden)

    M. T. Gargees

    2008-01-01

    Full Text Available Three experiments were conducted to elucidate the alleviation effects of Mycofix plus 3.0 on Newcastle antibody formation during aflatoxicosis in broiler chickens. Three levels of Mycofix (0.05%, 0.15%, and 0.25% and aflatoxin (2.5ppm, 3.5ppm, and 5ppm were used. Chickens were vaccinated at 8 and 18 days of age. Enzyme-linked immunosorbent assay and Haemagglutination inhibition tests were employed for determination Newcastle antibody titers at 28 days. The results showed that, Mycofix , and only at its high level of addition (0.25% was effective in ameliorating the negative effect of aflatoxin at the rates 2.5ppm and 3.5 ppm levels of inclusion on antibody production but not at the high level of 5ppm on antibody production, comparing with titers in control groups.

  14. Phase separation in solutions of monoclonal antibodies and the effect of human serum albumin

    OpenAIRE

    Wang, Ying; Lomakin, Aleksey; Latypov, Ramil F.; Benedek, George B.

    2011-01-01

    We report the observation of liquid-liquid phase separation in a solution of human monoclonal antibody, IgG2, and the effects of human serum albumin, a major blood protein, on this phase separation. We find a significant reduction of phase separation temperature in the presence of albumin, and a preferential partitioning of the albumin into the antibody-rich phase. We provide a general thermodynamic analysis of the antibody-albumin mixture phase diagram and relate its features to the magnitud...

  15. Antibody fluctuations of infected cattle with Fasciola gigantica and the effect of triclabendazole treatment

    Directory of Open Access Journals (Sweden)

    S Widjajanti

    2001-12-01

    Full Text Available Observation on the antibody fluctuations of infected cattle with metacercariae of Fasciola gigantica and the effect of triclabendazole treatment were made by means of ELISA technique. Seven cattle were infected with 700 metacercariae and one cattle remained uninfected, as negative control animal. Treatment with triclabendazole was given to 6 cattle, when the mean antibody levels of infected cattle reached the peak, and the other one remained untreated, as positive control animal. One week after treatment the mean antibody levels started to drop and then decreased gradually. After eight weeks of treatment, the mean antibody levels of the treated cattle reached the lowest level or the same value as before infection, thereafter, 6 cattle were reinfected with different dosages of metacercariae of F. gigantica. Two cattle were infected with 400 metacercariae, the other two were infected with 600 metacercariae and the rest of them were infected with 800 metacercariae. The results showed that the immunological responses of re-infected cattle are quicker (5 weeks after infection and the peak of the antibody levels are higher (ELISA OD = 1.7 than after the first infection (11 weeks after infection and ELISA OD = 1.2. However, after re-infection, there were no significant different on the antibody fluctuations and antibody levels among the infected group, although those cattle received different dosages.

  16. Effect of Central Antileptin Antibody on the Onset of Female Rat Puberty

    OpenAIRE

    Ruimin Chen; Gail J. Mick; Rongxian Xu; Daoxin Zheng; Yanfeng Fan; Xiangquan Lin; McCormick, Kenneth L.

    2009-01-01

    The effect of intracerebroventricular (ICV) antileptin antibody on the onset of puberty in the female rat and the relationship between serum leptin, luteinizing hormone (LH), and body weight were investigated. Antileptin antibody (group A) was infused ICV from days 23–36 in prepubertal female rats whereas the control (group B) received ICV goat immunoglobulin G (IgG). In the antileptin group, mean day of vaginal opening (VO) was postponed (day 34 versus day 30, P<.01 ). Body weig...

  17. Effects of Route of Inoculation and Viral Genetic Variation on Antibody Responses to Polyomavirus SV40 in Syrian Golden Hamsters

    OpenAIRE

    Swain, Jody L.; Sroller, Vojtech; Wong, Connie; Zhang, Shaojie; Halvorson, Steven J.; Herron, Alan J.; Kozinetz, Claudia A.; Butel, Janet S.

    2012-01-01

    Genetic variants of polyomavirus SV40 are powerful agents with which to define viral effects on cells and carcinogenesis pathways. We hypothesized that differences in biologic variation among viral strains affect the process of viral infection and are reflected in antibody responses to the viral nonstructural large T-antigen (TAg) protein but not in neutralizing antibody responses against the inoculated viral particles. We analyzed the production of TAg antibody and neutralizing antibody in S...

  18. Indocyanine green as effective antibody conjugate for intracellular molecular targeted photodynamic therapy

    Science.gov (United States)

    Wang, Sijia; Hüttmann, Gereon; Rudnitzki, Florian; Diddens-Tschoeke, Heyke; Zhang, Zhenxi; Rahmanzadeh, Ramtin

    2016-07-01

    The fluorescent dye indocyanine green (ICG) is clinically approved and has been applied for ophthalmic and intraoperative angiography, measurement of cardiac output and liver function, or as contrast agent in cancer surgery. Though ICG is known for its photochemical effects, it has played a minor role so far in photodynamic therapy or techniques for targeted protein-inactivation. Here, we investigated ICG as an antibody-conjugate for the selective inactivation of the protein Ki-67 in the nucleus of cells. Conjugates of the Ki-67 antibody TuBB-9 with different amounts of ICG were synthesized and delivered into HeLa and OVCAR-5 cells through conjugation to the nuclear localization sequence. Endosomal escape of the macromolecular antibodies into the cytoplasm was optically triggered by photochemical internalization with the photosensitizer BPD. The second light irradiation at 690 nm inactivated Ki-67 and subsequently caused cell death. Here, we show that ICG as an antibody-conjugate can be an effective photosensitizing agent. Best effects were achieved with 1.8 ICG molecules per antibody. Conjugated to antibodies, the ICG absorption peaks vary proportionally with concentration. The absorption of ICG above 650 nm within the optical window of tissue opens the possibility of selective Ki-67 inactivation deep inside of tissues.

  19. The Effect of Inflammatory Reactions on Antibody Unresponsiveness to Hepatitis B Vaccine in Hemodialysis Patients

    Directory of Open Access Journals (Sweden)

    Dede Sit et al.

    2007-01-01

    Full Text Available Background and Aims: In this study, the effect of infections and inflammation developed during hepatitis B vaccination program on antibody response in hemodialysis (HD patients was evaluated. Methods: In total, 94 patients who had hepatitis B surface antigen (HBsAg (-, antibody to hepatitis B surface (antiHBs (-, antibody against hepatitis B core immunoglobulin G (antiHBcIgG (- (Group A and who were previously vaccinated but having antibody titer levels lower than 10 mIU/mL (Group B, on maintenance HD program were included in this study. In group A, 40 |μ|g intramuscular vaccine on 0, 1, 2 and 6 months and in group B, 40 μ|g of intramuscular booster dose vaccine were administered. Antibody titer of 10 mIU/mL was considered as positive. Group A was then divided into two subgroups with respect to antibody response (Group A1 and Group A2. Results: Eighty-one patients completed the study (Group A; n=64, mean age=42.3±11.4 years; Group B: n=17, mean age=53.6±10.6 years. In Group A, antibody response was positive in 82.8% (Group A1, negative in 17.2% (Group A2 and it was positive in 100% of Group B. Inflammatory parameters, nutritional and demographic features were found similarly in all groups. Throughout the study, infections developed most frequently in Group A. Conclusions: We concluded that acute infections and inflammations developed in patients vaccinated according to vaccination schedule recommended for HBV prophylaxis during HD treatment does not affect antibody response and acute phase reactants are not indicators for negative antibody response.

  20. Synergistic cytotoxic effects of antibodies directed against different cell surface determinants

    International Nuclear Information System (INIS)

    Three antibody populations were raised in rabbits against surface antigens on guinea-pig L2C leukaemic lymphocytes: against idiotypic determinants on the lambda chain of the surface immunoglobulin, against C region determinants on the lambda chain, and against the surface antigens recognised by conventional anti-lymphocyte sera. Complement and K-cell cytotoxicities effected by the antibodies on L2C cells were studied in vitro. In both cytotoxic systems mixtures of the antibodies revealed synergy, in that the titres of the mixtures exceeded predicted additive titres of their components. The synergy was greater when the mixed antibodies were directed to determinants on the same molecule rather than to determinants on different molecules. (author)

  1. Serrumab: a human monoclonal antibody that counters the biochemical and immunological effects of Tityus serrulatus venom.

    Science.gov (United States)

    Pucca, Manuela Berto; Zoccal, Karina Furlan; Roncolato, Eduardo Crosara; Bertolini, Thaís Barboza; Campos, Lucas Benício; Cologna, Camila Takeno; Faccioli, Lúcia Helena; Arantes, Eliane Candiani; Barbosa, José Elpidio

    2012-01-01

    In Brazil, the species Tityus serrulatus is responsible for the most severe cases of scorpion envenomation. There is currently a need for new scorpion anti-venoms that are more effective and less harmful. This study attempted to produce human monoclonal antibodies capable of inhibiting the activity of T. serrulatus venom (TsV), using the Griffin.1 library of human single-chain fragment-variable (scFv) phage antibodies. Four rounds of phage antibody selection were performed, and the round with the highest phage antibody titer was chosen for the production of monoclonal phage antibodies and for further analysis. The scFv 2A, designated serrumab, was selected for the production and purification of soluble antibody fragments. In a murine peritoneal macrophage cell line (J774.1), in vitro assays of the cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 were performed. In male BALB/c mice, in vivo assays of plasma urea, creatinine, aspartate transaminase, and glucose were performed, as well as of neutrophil recruitment and leukocyte counts. It was found that serrumab inhibited the TsV-induced increases in the production of IL-6, TNFα, and IL-10 in J774.1 cells. The in vivo inhibition assay showed that serrumab also prevented TsV-induced increases in the plasma levels of urea, creatinine, aspartate transaminase, and glucose, as well as preventing the TsV-induced increase in neutrophil recruitment. The results indicate that the human monoclonal antibody serrumab is a candidate for inclusion in a mixture of specific antibodies to the various toxins present in TsV. Therefore, serrumab shows promise for use in the production of new anti-venom. PMID:22424317

  2. Model system that predicts effective half-life for radiolabeled antibody therapy

    International Nuclear Information System (INIS)

    Radiolabeled antibodies to tumor associated proteins localize in both experimental and clinical cancers. In the therapeutic applications of radiolabeled antibody, tumor effective half-life along with the concentration of isotope deposited and energies of the isotope used, determine the tumor dose. Antibodies directed against the same antigenic specificity but derived from different species have varied tumor and whole body effective half-lives and as a result, achieve different tumor doses. In vitro testing does not evaluate the in vivo differences in effective half-life that affect tumor dose. The authors have developed an animal model to evaluate the effective half-live and biodistribution of radiolabeled immunoglobulin (IgG) from diverse species. In both the experimental model and in the clinical trials, radiolabeled immunospecific and normal IgG derived from monkey, rabbit, and porcine sources had the longest effective half-lives, goat and sheep had intermediate effective half-lives, and chicken and turkey had the shortest effective half-lives. These species have been immunized for clinical use. The value of this model system is that it appears to be an effective in vivo preclinical screen for tumor effective half-live of antibodies and IgG from diverse species, thus guiding potential clinical use

  3. Effects of X irradiation on homocytotropic and agglutinating antibody production in mice

    International Nuclear Information System (INIS)

    The effect of X irradiation on homocytotropic and agglutinating antibody production was studied in mice exposed to 400 rad either before or after immunization with dinitrophenylated Ascaris plus aluminium hydroxide as adjuvant. The adjuvant effect of irradiation was also determined in animals receiving antigen alone. Irradiation 1 day before immunization with adjuvant enhanced IgE and slightly enhanced IgM-antibody formation, although the onset was delayed, but partially suppressed IgG-antibody formation. When the same treatment followed antigen priming, there was a similar enhancement of IgE production which varied with the time between the two procedures. IgG and IgM production, however, were fairly resistant under the same conditions. Irradiation preceding immunization with soluble antigen had no significant adjuvant effect on IgE-, IgG- or IgM-antibody production. On the contrary, it suppressed production of the latter two classes. The results may indicate that production of IgE and of IgG and IgM antibodies in the mouse is regulated by separate mechanisms. (author)

  4. Stability of 188Re Labeled antibody for radioimmunotherapy and the effect of stabilizing agents

    International Nuclear Information System (INIS)

    For clinical application of beta-emitter labeled antibody, high specific activity is important. Carrier-free 188Re from 188W/ 188Re generator is an ideal radionuclide for this purpose. However, low stability of 188Re labeled antibody, especially in high specific activity, due to radiolytic decomposition by high energy (2.1 MeV) beta ray was problem. We studied the stability of 188Re labeled antibody, and stabilizing effect of several stabilizers. Pre-reduced monoclonal antibody (CEA79.4) was labeled with 188Re by incubating with generator-eluted 188Re-perrhenate in the presence of stannous tartrate for 2 hr at room temperature. Radiochemical purity of each preparation was determined by chromatography. Human serum albumin was added to the labeled antibodies (2%). Stability of 188Re-CEA79.4 was investigated in the presence of ascorbic acid, ethanol, or Tween 80 as stabilizing agents. Labeling efficiencies were 88±4% (n=12). Specific activities of 1.25 ∼4.77 MBq/μg were obtained. If stored after purging with N2, all the preparations were stable for 10 hr. However, stability decreased in the presence of air. Perrhenate and 188Re-tartrate was major impurity in declined preparation. Colloid-formation was not a significant problem in all cases. Addition of ascorbic acid stabilized the labeled antibodies either under N2 or under air by reducing the formation of perrhenate. High specific activity 188Re labeled antibody is unstable, especially, in the presence of oxygen. Addition of ascorbic acid increased the stability

  5. Clonal relationships between thyroid-stimulating hormone receptor-stimulating antibodies illustrate the effect of hypermutation on antibody function

    DEFF Research Database (Denmark)

    Padoa, Carolyn J; Larsen, Sanne L; Hampe, Christiane S;

    2009-01-01

    Summary Graves' disease is characterized by production of agonist antibodies to the thyroid-stimulating hormone receptor (TSHR), but knowledge of the genetic and somatic events leading to their aberrant production is limited. We describe the genetic analysis of two monoclonal antibodies (mAbs) with......-determining regions (CDRs) and the framework regions. The cloned IGHV and IGLV genes were confirmed to have TSAb properties in experiments in which they were expressed as recombinant Fabs (rFabs). In other experiments, we swapped the IGLV genes with IGHV genes by constructing chimeric rFabs and showed that the...... experimentally immunized mice, multiple pathogenic antibodies to TSHR can arise from a single clone by a series of somatic mutations in the V-region genes and may give an insight into how such antibodies develop spontaneously in autoimmune Graves' disease....

  6. Whole-body effective half-lives for radiolabeled antibodies and related issues

    Energy Technology Data Exchange (ETDEWEB)

    Kaurin, D.G.L.; Carsten, A.L.; Baum, J.W.; Barber, D.E.

    1996-08-01

    Radiolabeled antibodies (RABs) are being developed and used in medical imaging and therapy in rapidly increasing numbers. Data on the whole body half effective half-lives were calculated from external dose rates obtained from attending physicians and radiation safety officers at participating institutions. Calculations were made using exponential regression analysis of data from patients receiving single and multiple administrations. Theses data were analyzed on the basis of age, sex, isotope label, radiation energy, antibody type, disease treated, administration method, and number of administrations.

  7. Whole-body effective half-lives for radiolabeled antibodies and related issues

    International Nuclear Information System (INIS)

    Radiolabeled antibodies (RABs) are being developed and used in medical imaging and therapy in rapidly increasing numbers. Data on the whole body half effective half-lives were calculated from external dose rates obtained from attending physicians and radiation safety officers at participating institutions. Calculations were made using exponential regression analysis of data from patients receiving single and multiple administrations. Theses data were analyzed on the basis of age, sex, isotope label, radiation energy, antibody type, disease treated, administration method, and number of administrations

  8. Effects of Temperature on Production and Specificity of Antibodies in Rainbow Trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Mikkelsen, Heidi; Nielsen, Michael Engelbrecht; Lindenstrom, Thomas

    2006-01-01

    The effect of temperature on production and affinity of antibodies against antigens from the parasitic ciliate Ichthyophthirius multifiliis were studied in rainbow trout (Oncorhynchus mykiss). Fish were immunized with I. multifiliis antigens and reared at three different temperatures, 5, 12, and ...

  9. Effect of high mannose glycan pairing on IgG antibody clearance.

    Science.gov (United States)

    Liu, Yaoqing Diana; Flynn, Gregory C

    2016-05-01

    IgG antibodies contain N-linked glycans on the Fc portion of each heavy chain. The glycan on one heavy chain can either match the glycan on the other heavy chain (symmetrical pairing) or be different (asymmetrical pairing). These Fc glycans influence effector functions and can alter clearance rates. Previous studies showing that high mannose forms result in faster mAb clearance in humans were incapable of differentiating the impact of symmetrically vs. asymmetrically paired HM forms, and, therefore, the effect of pairing on clearance was not clear. Traditional analytical methods, which are used to measure glycans in such studies, do not determine the number of HM glycans per antibody. With a sensitive method designed to measure HM pairing, we followed the levels of symmetrically and asymmetrically paired HM on antibodies in human pharmacokinetic serum samples to determine the impact of Fc HM glycan pairing on therapeutic human IgG clearance in humans. The two HM paired forms cleared at the same rate, indicating that the effect on clearance was not proportional to the degree of modification. Since both forms can exist on therapeutic antibodies and the ratio can differ between products, measuring their relative levels is necessary to properly estimate effects on clearance. PMID:26992607

  10. Effect of monoclonal antibodies on limited proteolysis of native glycoprotein gD of herpes simplex virus type 1

    International Nuclear Information System (INIS)

    We examined the properties of 17 monoclonal antibodies to glycoprotein gD of herpes simplex type 1 (HSV-1) (gD-1) and HSV-2 (gD-2). The antibodies recognized eight separate determinants of gD, based on differences in radioimmuno-precipitation and neutralization assays. The determinants were distributed as follows: three were gD-1 specific, one was gD-2 specific, and four were type common. Several type-specific and type-common determinants appeared to be involved in neutralization. We developed a procedure for examining the effect that binding of monoclonal antibody has on proteolysis of native gD-1 by Staphylococcus aureus protease V8. We showed that several different patterns of protease V8 cleavage were obtained, depending on the monoclonal antibody used. The proteolysis patterns were generally consistent with the immunological groupings. With four groups of antibodies, we found that fragments of gD-1 remained bound to antibody after V8 treatment. A 38,000-dalton fragment remained bound to antibodies in three different groups of monoclonal antibodies. This fragment appeared to contain one type-common and two type-specific determinants. A 12,000-dalton fragment remained bound to antibodies belonging to one type-common group of monoclonal antibodies. Tryptic peptide analysis revealed that the 12,000-dalton fragment represented a portion of the 38,000-dalton fragment and was enriched in a type-common arginine tryptic peptide

  11. Evaluation of thyroid antibodies and benign disease prevalence among young adults exposed to (131)I more than 25 years after the accident at the Chernobyl Nuclear Power Plant.

    Science.gov (United States)

    Kimura, Yuko; Hayashida, Naomi; Takahashi, Jumpei; Rafalsky, Ruslan; Saiko, Alexsey; Gutevich, Alexander; Chorniy, Sergiy; Kudo, Takashi; Takamura, Noboru

    2016-01-01

    Background. The Chernobyl Nuclear Power Plant (CNPP) accident exposed a large number of inhabitants to internal (131)I radiation. The associations between internal (131)I exposure and thyroid autoimmunity and benign thyroid diseases remain controversial in the population living in the contaminated area around the CNNP. In this study, we evaluate the association of (131)I with benign thyroid diseases. Methods. We compared the prevalence of Anti-Thyroid Autoantibodies (ATAs), thyroid function, and prevalence of thyroid ultrasound finding outcomes in 300 residents of the contaminated area of Ukraine who were 0-5 years of age at the time of the CNPP accident (group 1) and 300 sex-matched residents who were born after the accident (group 2). Results. We did not find any differences of the prevalence of Antithyroglobulin Antibodies (TGAb) positive, Antithyroid Peroxidase Antibodies (TPOAb) positive, and TGAb and/or TPOAb positive between the study groups. (11.7% vs 10.3%; p = 0.602, 17.3% vs 13.0%; p = 0.136, 21.0% vs 17.3%; p = 0.254, respectively); after adjusting for age and sex, the prevalence was not associated with the (131)I exposure status in the study groups. The prevalence of subclinical and overt hypothyroidism cases was not significantly different (p = 0.093 and p = 0.320) in the two groups, nor was the prevalence of goiter (p = 0.482). On the other hand, the prevalence of nodules was significantly higher in group 1 (p = 0.003), though not significantly so after adjustment for age and sex. Discussion. Working 26-27 years after the CNNP accident, we found no increased prevalence of ATAs or benign thyroid diseases in young adults exposed to (131)I fallout during early childhood in the contaminated area of Ukraine. Long-term follow-up is needed to clarify the effects of radiation exposure on autoimmunity reaction in the thyroid. PMID:27019779

  12. Evaluation of thyroid antibodies and benign disease prevalence among young adults exposed to 131I more than 25 years after the accident at the Chernobyl Nuclear Power Plant

    Science.gov (United States)

    Kimura, Yuko; Hayashida, Naomi; Takahashi, Jumpei; Rafalsky, Ruslan; Saiko, Alexsey; Gutevich, Alexander; Chorniy, Sergiy; Kudo, Takashi

    2016-01-01

    Background. The Chernobyl Nuclear Power Plant (CNPP) accident exposed a large number of inhabitants to internal 131I radiation. The associations between internal 131I exposure and thyroid autoimmunity and benign thyroid diseases remain controversial in the population living in the contaminated area around the CNNP. In this study, we evaluate the association of 131I with benign thyroid diseases. Methods. We compared the prevalence of Anti-Thyroid Autoantibodies (ATAs), thyroid function, and prevalence of thyroid ultrasound finding outcomes in 300 residents of the contaminated area of Ukraine who were 0–5 years of age at the time of the CNPP accident (group 1) and 300 sex-matched residents who were born after the accident (group 2). Results. We did not find any differences of the prevalence of Antithyroglobulin Antibodies (TGAb) positive, Antithyroid Peroxidase Antibodies (TPOAb) positive, and TGAb and/or TPOAb positive between the study groups. (11.7% vs 10.3%; p = 0.602, 17.3% vs 13.0%; p = 0.136, 21.0% vs 17.3%; p = 0.254, respectively); after adjusting for age and sex, the prevalence was not associated with the 131I exposure status in the study groups. The prevalence of subclinical and overt hypothyroidism cases was not significantly different (p = 0.093 and p = 0.320) in the two groups, nor was the prevalence of goiter (p = 0.482). On the other hand, the prevalence of nodules was significantly higher in group 1 (p = 0.003), though not significantly so after adjustment for age and sex. Discussion. Working 26–27 years after the CNNP accident, we found no increased prevalence of ATAs or benign thyroid diseases in young adults exposed to 131I fallout during early childhood in the contaminated area of Ukraine. Long-term follow-up is needed to clarify the effects of radiation exposure on autoimmunity reaction in the thyroid. PMID:27019779

  13. Effects of Anti-Caries Antibodies on Lactobacillus GG in Its Fermentation and Storage Periods

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective To investigate how antibodies influence the fermentation of Lactobacillus GG and how Lactobacillus GG influences the biological properties of antibodies during the fermentation and storage periods. Methods Anti-caries immune colostrum powder (IP) and control colostrum powder (CP), skimmed milk powder (SP) at concentrations of 1%, 2.5%, 5% and 10% (w/v) were added to MRS and 50mM Hepes buffer system was used in the milk, the growth curves of Lactobacillus GG including viable cells, lactic acid concentatrion and pH, and also the titer of specific antibodies were determined during the fermentation and storage periods. Results In MRS, SP could improve the growth of Lactobacillus GG in all periods of fermentation, especially at the concentrations of 5% and 10%. CP at the concentrations of 1% and 2.5% had a good initial velocity at the beginning and CP (1%, 2.5%, 5%, 10%) in all the groups could reach a high viable cell concentration at the end of fermentation, which suggested that there were some growth factors for Lactobacillus GG in CP overcoming the inhibition of unspecific antibodies. IP at 1%, 2.5%, 5% and 10% could inhibit the growth of Lactobacillus GG in all the fermentation periods, the critical concentration point was between 2.5%-5%, and there was a competition between growth factors and the inhibition of specific antibodies. In pasteurized milk, the influence of Hepes could help the fermentation start quickly and reach the log phase earlier than in the control group; however, when combined with 5% IP, the growth of Lactobacillus GG was strongly inhibited during all the fermentation periods. The fermentation of Lactobacillus GG had no significant effect on the titer change of anti-caries antibodies during the fermentation and storage periods. Conclusion SP and CP is beneficial to the growth of Lactobacillus GG in MRS, whereas there is a competition between growth factors and the inhibition of specific antibodies to the growth of Lactobacillus GG

  14. The effect of anti-human plasminogen monoclonal antibodies on Glu-plasminogen activation by plasminogen activators

    Directory of Open Access Journals (Sweden)

    M. Akrami

    2006-07-01

    Full Text Available Background: Human plasminogen is a plasma glycoprotein synthesized mainly in the liver. Conversion of plasminogen to plasmin by plasminogen activators is a key event in the fibrinolytic system. In this study, we investigated the effects of two anti-human plasminogen monoclonal antibodies, A1D12 and MC2B8 on Glu-plasminogen activation in presence of u-PA, t-PA and streptokinase. Methods: Producing of Hybridoma antibodies was performed by fusion of spleen cells from BALB/C mice immunized with Glu-plasminogen and NS1 myeloma cells. Antibody binding to Human Glu-plasminogen was assessed using an ELISA assay. Activation of plasminogen was determined by measuring plasmin generation using the chromogenic substrate S-2251 and the effect of monoclonal antibodies, A1D12 and MC2B8 on plasminogen activation in solution was then evaluated. Initial rates and kinetic parameters of plasminogen activation in the presence of monoclonal antibodies were calculated. The effect of the monoclonal antibody MC2B8 on the rate of plasmin hydrolysis was measured. The effect of F(ab'2 fragment of A1D12 on u-PA catalyzed-plasminogen activation also compared with the effect of the whole antibody in this reaction. Results: ELISA assay showed that the antibodies reacted well with antigens. A1D12 increased the maximum velocity (Vmax of plasminogen activation by each of the three plasminogen activators and MC2B8 decreased it. In all activation reactions, the KM value of plasminogen activation did not significantly change in the presence of antibody A1D12 whereas antibody MC2B8 increased the KM value of plasminogen activation by u-PA, fibrin monomer dependent t-PA and streptokinase. Monoclonal antibody MC2B8 had no significant effect on plasmin hydrolysis rate of synthetic substrate S-2251. Activation rate of plasminogen by u-PA in the lower concentration of F (ab2 fragment of A1D12 was identical to activation in the presence of the whole antibody. Conclusion: The binding of

  15. Effect of different hapten-carrier conjugation ratios and molecular orientations on antibody affinity against a peptide antigen

    DEFF Research Database (Denmark)

    Pedersen, M. K.; Sørensen, Nanna Skall; Heegaard, Peter M. H.;

    2006-01-01

    affinity and titre of antibodies raised against the hapten using different conjugation ratios and orientations. The peptide was coupled to ovalbumin in four Conjugation ratios and two molecular orientations - terminal and central - and the Conjugates were verified by mass spectrometry. Mice were immunised....... Furthermore, the molecular orientation of the Coupled peptide has a major effect on the anti-peptide antibody titres induced....

  16. Effects of interlinker sequences on the biological properties of bispecific single-chain antibodies

    Institute of Scientific and Technical Information of China (English)

    FANG Min; JIANG Xin; YANG Zhi; YIN Changcheng; LI Hua; ZHAO Rui; ZHANG Zhong; LIN Qing; HUANG Hualiang

    2003-01-01

    Single-chain bispecific antibody (scBsAb) is one of the promising genetic engineering antibody formats for clinical application. But the effects of interlinker sequences on the biological properties of bispecific single-chain antibodies have not been studied in detail. Three interlinker sequences were designed and synthesized, and denominated as Fc, HSA, 205C′, respectively. Universal vectors with these different interlinker sequences for scBsAb expression in E. coli were constructed. A model scBsAb based on a reshaped single-chain antibody (scFv) against human CD3 and a scFv directed against human ovarian carcinoma were generated and expressed in E. coli. The results of SDS-PAGE and Western blot showed that the different interlinker sequences did not affect the expression levelof scBsAb. However, as demonstrated by ELISA and pharmacokinetics studies performed in mice, scBsAbs with different interlinker sequences had difference in the antigen-binding activities and terminal half-life time (T1/2β) in vivo, the interlinker HSA could remarkably prolong the retention time of scBsAb in blood. These results indicated that the peptide sequence of interlinker could affect important biological properties of scBsAb, such as antigen-binding properties and stability in vivo. So, selection of an appropriate interlinker sequence is very important for scBsAb construction. Optimal interlinker can bring scBsAb biologicalproperties more suitable for clinical application.

  17. Effect of low dose gamma-radiation upon Newcastle disease virus antibody level in chicken

    International Nuclear Information System (INIS)

    The specific antibody response against Newcastle disease virus in the blood serum of chickens hatched from eggs exposed to low dose gamma-radiation was studied. Materials and methods: Two groups of eggs of commercial meat chicken lines were irradiated with the dose of 0.30 Gy 60Co gamma-rays before incubation and on the 19th day of incubation, respectively. The same number of eggs unexposed to gamma-radiation served as controls. After hatching the group of chicken hatched from eggs irradiated on the 19th day of incubation was not vaccinated while the group of chicken hatched from eggs irradiated before incubation was vaccinated on the 14 day. Specific serum anti-Newcastle disease virus antibodies were quantified by the hemagglutination inhibition assay with 4 HA units of Newcastle disease virus La Sota strain. Result: Specific antibody titres against Newcastle disease virus in the blood serum of chickens hatched from eggs irradiated before incubation and vaccinated on the 14th day significantly increased on the 28th day. Specific antibody titre against Newcastle disease virus in the blood serum of chickens hatched from eggs irradiated on the 19th day of incubation and non-vaccinated was significantly higher on the 1st and 14th day. Conclusion: Acute irradiation of heavy breeding chicken eggs with the dose of 0.30 Gy 60Co gamma-rays before incubation and on the 19th day of incubation could have a stimulative effect on humoral immunity in chickens.

  18. [Mechanisms of the stimulating effect of brain antibodies on the Ca2 current in the neuron membrane].

    Science.gov (United States)

    Solntseva, E I; Pozdniakova, A L; Savich, V; Khorvat, I; Iankovich, B

    1987-11-01

    Antibodies against rat brain microsomes induce a 16 +/- 3% increase in the amplitude of Ca-current (ICa) in snail neurons. Ca-ions block ICa in dose-dependent and potential-dependent manner. Antibodies against microsomes decrease the effectiveness of ICa blockade by Ca-ions: a 85 +/- 10% increase in ICa is observed and I-V curve is normalized. It is suggested that an enhancing effect of antibodies on ICa and the elimination of blocking Ca-effect on ICa are connected with the weakening of divalent cations binding by the anionic groups of calcium channels. PMID:2445395

  19. Thyroid Antibodies

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Thyroid Antibodies Share this page: Was this page helpful? Also known as: Thyroid Autoantibodies; Antithyroid Antibodies; Antimicrosomal Antibody; Thyroid Microsomal Antibody; ...

  20. Structure-based, targeted deglycosylation of HIV-1 gp120 and effects on neutralization sensitivity and antibody recognition

    International Nuclear Information System (INIS)

    The human immunodeficiency virus (HIV-1) exterior envelope glycoprotein, gp120, mediates receptor binding and is the major target for neutralizing antibodies. Primary HIV-1 isolates are characteristically more resistant to broadly neutralizing antibodies, although the structural basis for this resistance remains obscure. Most broadly neutralizing antibodies are directed against functionally conserved gp120 regions involved in binding to either the primary virus receptor, CD4, or the viral coreceptor molecules that normally function as chemokine receptors. These antibodies are known as CD4 binding site (CD4BS) and CD4-induced (CD4i) antibodies, respectively. Inspection of the gp120 crystal structure reveals that although the receptor-binding regions lack glycosylation, sugar moieties lie proximal to both receptor-binding sites on gp120 and thus in proximity to both the CD4BS and the CD4i epitopes. In this study, guided by the X-ray crystal structure of gp120, we deleted four N-linked glycosylation sites that flank the receptor-binding regions. We examined the effects of selected changes on the sensitivity of two prototypic HIV-1 primary isolates to neutralization by antibodies. Surprisingly, removal of a single N-linked glycosylation site at the base of the gp120 third variable region (V3 loop) increased the sensitivity of the primary viruses to neutralization by CD4BS antibodies. Envelope glycoprotein oligomers on the cell surface derived from the V3 glycan-deficient virus were better recognized by a CD4BS antibody and a V3 loop antibody than were the wild-type glycoproteins. Absence of all four glycosylation sites rendered a primary isolate sensitive to CD4i antibody-mediated neutralization. Thus, carbohydrates that flank receptor-binding regions on gp120 protect primary HIV-1 isolates from antibody-mediated neutralization

  1. Effects of various application routes of Newcastle disease vaccine on specific antibody titres in ostriches

    Directory of Open Access Journals (Sweden)

    Lukač-Novak Irena

    2008-01-01

    Full Text Available Newcastle disease (ND is one of the most important diseases of poultry and other avian species. The usual mean to control ND is specific immunoprophylaxis. Although chickens are routinely vaccinated against ND, vaccination of ostriches is less well understood. We investigated the effect of vaccination against Newcastle disease via different routes on specific antibody titer in 24 adult ostriches, divided into three experimental and one control group. The vaccine was administered in drinking water to the first, by spraying to the second, and oculo-nasally to the third group. The results have indicated antibody production with titers sufficient for humoral immunity in all experimental groups. The strongest immune response was determined in the group vaccinated by spraying. .

  2. Effect of Central Antileptin Antibody on the Onset of Female Rat Puberty

    Directory of Open Access Journals (Sweden)

    Fan Yanfeng

    2009-08-01

    Full Text Available The effect of intracerebroventricular (ICV antileptin antibody on the onset of puberty in the female rat and the relationship between serum leptin, luteinizing hormone (LH, and body weight were investigated. Antileptin antibody (group A was infused ICV from days 23–36 in prepubertal female rats whereas the control (group B received ICV goat immunoglobulin G (IgG. In the antileptin group, mean day of vaginal opening (VO was postponed (day 34 versus day 30, . Body weight trended higher after 30 days in the antileptin group but not significantly. However, there was no difference in serum leptin and LH between the two groups on the day of VO. Serum leptin was relatively constant from day 23 through day 31 and did not correlate with LH . These studies demonstrate that central leptin promotes the onset of female rat puberty as evidenced by VO. Finally, central leptin impacts female rat pubertal onset in distinction from serum leptin and body weight.

  3. Effect of inoculation route on the production of antibodies and histological characteristics of the spleen in laying hens

    Directory of Open Access Journals (Sweden)

    SF Eto

    2012-03-01

    Full Text Available Recent studies have reported the use of IgY antibody in the prevention or treatment of diseases in animals. IgY can be obtained in large amounts from the yolk of chicken eggs through a low-cost process. This study evaluated the effect of different routes of inoculation on antibody production and spleen morphological characteristics of laying hens (White Leghorn inoculated with sheep red blood cells. The analysis of the results showed that the intramuscular route is the most efficient for total antibody production in the primary immune response, while the intravenous route is the most efficient in producing IgY antibodies in the secondary immune response. No histological changes were observed in the spleen of laying hens. This study could be useful for developing protocols of antigen inoculation in laying hens for IgY antibody production.

  4. ADVERSE EFFECTS OF INTRAVENOUS IMMUNOGLOBULIN THERAPY IN PATIENTS WITH ANTIBODY DEFICIENCY

    Directory of Open Access Journals (Sweden)

    A. Aghamohammadi

    2003-09-01

    Full Text Available Long-term intravenous immunoglobulin (IVIG infusion is an effective treatment for children with humoral immunodeficiencies, already be complicated by systemic ad¬verse effects. In order to determine the adverse effects of intravenous immunoglobulin inpatients with antibody deficiency, 45 immunodeficientpatients receiving intravenous immunoglobulin were studied during a 36-month period at Children's Medical Center. The investigated group included 25 patients with common variable immunodeficiency, 14 patients with X-linked agammaglobulinemia and 6 patients with IgG subclass defi¬ciency. A total of fifty adverse effects occurred through 955 infusions (5.2%. The most frequent immediate adverse effects were mild (40 infusions out of 955 in 22 cases, including: chills, flushing, fever, nausea and headache. Three patients experienced mod¬erate effects (10 infusions out of 955 such as rash, severe headache, joint pain and chest tightness. None of the effects was anaphylactic type. It can be concluded that intravenous immunoglobulin is generally a well-tolerated medical agent for patients with antibody deficiency, but all patients should be monitored by a physician who is familiar with its indications, risks, adverse effects and their appropriate management.

  5. A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion.

    Science.gov (United States)

    Shi, Xin; Deng, Yongqiang; Wang, Huajing; Ji, Guanghui; Tan, Wenlong; Jiang, Tao; Li, Xiaofeng; Zhao, Hui; Xia, Tian; Meng, Yanchun; Wang, Chao; Yu, Xiaojie; Yang, Yang; Li, Bohua; Qin, E-De; Dai, Jianxin; Qin, Cheng-Feng; Guo, Yajun

    2016-01-01

    Although dengue virus (DENV) infection severely threatens the health of humans, no specific antiviral drugs are currently approved for clinical use against DENV infection. Attachment and fusion are 2 critical steps for the flavivirus infection, and the corresponding functional epitopes are located at E protein domain III (E-DIII) and domain II (E-DII), respectively. Here, we constructed a bispecific antibody (DVD-1A1D-2A10) based on the 2 well-characterized anti-DENV monoclonal antibodies 1A1D-2 (1A1D) and 2A10G6 (2A10). The 1A1D antibody binds E-DIII and can block the virus attaching to the cell surface, while the 2A10 antibody binds E-DII and is able to prevent the virus from fusing with the endosomal membrane. Our data showed that DVD-1A1D-2A10 retained the antigen-binding activity of both parental antibodies. Importantly, it was demonstrated to be significantly more effective at neutralizing DENV than its parental antibodies both in vitro and in vivo, even better than the combination of them. To eliminate the potential antibody-dependent enhancement (ADE) effect, this bispecific antibody was successfully engineered to prevent Fc-γ-R interaction. Overall, we generated a bispecific anti-DENV antibody targeting both attachment and fusion stages, and this bispecific antibody broadly neutralized all 4 serotypes of DENV without risk of ADE, suggesting that it has great potential as a novel antiviral strategy against DENV. PMID:26905804

  6. Effect of influenza A/equine/H3N8 virus isolate variation on the measurement of equine antibody responses.

    OpenAIRE

    Bogdan, J R; Morley, P S; Townsend, H G; Haines, D M

    1993-01-01

    This study has tested the effect of using homologous or heterologous equine influenza A virus isolates to evaluate serum antibody levels to influenza A virus in vaccinated and naturally-infected horses. In addition, the potential effect of antigenic selection of virus variants in egg versus tissue culture propagation systems was studied. Serum antibody levels in samples from horses recently infected with a local influenza A virus isolate (A/equine 2/Saskatoon/1/90) or recently vaccinated with...

  7. Effect of inhibin gene immunization on antibody production and reproductive performance in Partridge Shank hens.

    Science.gov (United States)

    Mao, Dagan; Bai, Wujiao; Hui, Fengming; Yang, Liguo; Cao, Shaoxian; Xu, Yinxue

    2016-04-01

    To investigate the effect of inhibin gene immunization on antibody production and reproductive performance in broiler breeder females, Partridge Shank hens aged 380 days were immunized with inhibin recombinant plasmid pcISI. One hundred and twenty hens were randomly assigned to four groups and treated intramuscularly with 25, 75, or 125 μg/300-μL inhibin recombinant plasmid pcISI (T1∼T3) or 300-μL saline as control (C), respectively. Booster immunization was given with the same dosage 20 days later. Blood and egg samples were collected to detect the antibody against inhibin by enzyme-linked immunosorbent assay and to evaluate egg performance. The ovaries were collected to classify the follicles and detect the FSH receptor (FSHR) messenger RNA (mRNA) expression by reverse transcription-PCR. The results showed that immunization against pcISI could elicit antibody against inhibin in both plasma and egg yolk compared with the control (P lay during the first 30 days after primary vaccination (P laying performance in Partridge Shank hens, which provides a good foundation for the application of inhibin DNA vaccine in avian production. PMID:26739531

  8. Effect of Ozone Produced from Antibody-catalyzed Water Oxidation on Pathogenesis of Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    Ke-Jun PENG; Yu-Shan HUANG; Li-Na AN; Xiao-Qun HAN; Jing-Ge ZHANG; Qiu-Lin WANG; Jing SUN; Shu-Ren WANG

    2006-01-01

    Recent studies have suggested that antibodies can catalyze the generation of unknown oxidants including hydrogen peroxide (H2O2) and ozone (O3) from singlet oxygen (1O2) and water. This study is aimedto detect the effect of antibody-catalyzed water oxidation on atherosclerosis. Our results showed that both H2O2 and O3 were produced in human leukemia THP- 1 monocytes incubated with human immunoglobulin G and phorbol myristate acetate. In the THP-1 monocytes incubated with human immunoglobulin G, phorbol myristate acetate and low density lipoprotein, the intracellular total cholesterol, free cholesterol, cholesteryl ester and lipid peroxides clearly increased, and a larger number of foam cells were observed by oil red O staining. The accumulation of all intracellular lipids was significantly inhibited by vinylbenzoic acid, and only slightly affected by catalase. These findings suggested that the production of O3, rather than H2O2, might be involved in the pathogenesis of atherosclerosis through the antibody-catalyzed water oxidation pathway.

  9. Cellular cooperation during in vivo anti-hapten antibody responses. I. The effect of cell number on the response

    International Nuclear Information System (INIS)

    Cellular interactions in adoptive secondary anti-hapten antibody responses to the hapten 2,4-dinitrophenyl (DNP) have been studied. It was shown that DNP-specific B cells must interact with carrier specific helper T cells to give optimal responses. Independent titration of B cell and helper cell activity in adoptive anti-DNP antibody responses gave the following results: Doubling the number of transferred B cells approximately doubled the subsequent antibody response. Doubling the number of helper cells leads to nearly 4 times as much anti-DNP antibody, measured 7 days after boosting (''premium effect''). This marked effect of helper cell number on the antibody response is thought to be due primarily to the interaction of two populations of carrier-specific cells in the helper effect, or to the interaction of two activities of a single population of helper cells, namely clone activation and clone expansion. Only a very small proportion of the premium effect given by helper cells could be attributed to increases in antibody affinity. (U.S.)

  10. Effective chemoimmunotherapy with anti-TGFβ antibody and cyclophosphamide in a mouse model of breast cancer.

    Directory of Open Access Journals (Sweden)

    Xin Chen

    Full Text Available TGFβ is reportedly responsible for accumulation of CD4(+Foxp3(+ regulatory T cells (Tregs in tumor. Thus, we treated mouse 4T1 mammary carcinoma with 1D11, a neutralizing anti-TGFβ (1,2,3 antibody. The treatment delayed tumor growth, but unexpectedly increased the proportion of Tregs in tumor. In vitro, 1D11 enhanced while TGFβ potently inhibited the proliferation of Tregs. To enhance the anti-tumor effects, 1D11 was administered with cyclophosphamide which was reported to eliminate intratumoral Tregs. This combination resulted in long term tumor-free survival of up to 80% of mice, and the tumor-free mice were more resistant to re-challenge with tumor. To examine the phenotype of tumor infiltrating immune cells, 4T1-tumor bearing mice were treated with 1D11 and a lower dose of cyclophosphamide. This treatment markedly inhibited tumor growth, and was accompanied by massive infiltration of IFNγ-producing T cells. Furthermore, this combination markedly decreased the number of splenic CD11b(+Gr1(+ cells, and increased their expression levels of MHC II and CD80. In a spontaneous 4T1 lung metastasis model with resection of primary tumor, this combination therapy markedly increased the survival of mice, indicating it was effective in reducing lethal metastasis burden. Taken together, our data show that anti-TGFβ antibody and cyclophosphamide represents an effective chemoimmunotherapeutic combination.

  11. Effective chemoimmunotherapy with anti-TGFβ antibody and cyclophosphamide in a mouse model of breast cancer.

    Science.gov (United States)

    Chen, Xin; Yang, Yuan; Zhou, Qiong; Weiss, Jonathan M; Howard, Olamae Zack; McPherson, John M; Wakefield, Lalage M; Oppenheim, Joost J

    2014-01-01

    TGFβ is reportedly responsible for accumulation of CD4(+)Foxp3(+) regulatory T cells (Tregs) in tumor. Thus, we treated mouse 4T1 mammary carcinoma with 1D11, a neutralizing anti-TGFβ (1,2,3) antibody. The treatment delayed tumor growth, but unexpectedly increased the proportion of Tregs in tumor. In vitro, 1D11 enhanced while TGFβ potently inhibited the proliferation of Tregs. To enhance the anti-tumor effects, 1D11 was administered with cyclophosphamide which was reported to eliminate intratumoral Tregs. This combination resulted in long term tumor-free survival of up to 80% of mice, and the tumor-free mice were more resistant to re-challenge with tumor. To examine the phenotype of tumor infiltrating immune cells, 4T1-tumor bearing mice were treated with 1D11 and a lower dose of cyclophosphamide. This treatment markedly inhibited tumor growth, and was accompanied by massive infiltration of IFNγ-producing T cells. Furthermore, this combination markedly decreased the number of splenic CD11b(+)Gr1(+) cells, and increased their expression levels of MHC II and CD80. In a spontaneous 4T1 lung metastasis model with resection of primary tumor, this combination therapy markedly increased the survival of mice, indicating it was effective in reducing lethal metastasis burden. Taken together, our data show that anti-TGFβ antibody and cyclophosphamide represents an effective chemoimmunotherapeutic combination. PMID:24416401

  12. Individual and combining effects of anti-RANKL monoclonal antibody and teriparatide in ovariectomized mice

    Directory of Open Access Journals (Sweden)

    Naoto Tokuyama

    2015-06-01

    Full Text Available We examined the individual and combined effects of teriparatide and anti-RANKL (receptor activator of nuclear factor κB ligand monoclonal antibody in ovariectomized mice. Three-month-old female C57BL/6 mice were ovariectomized (OVX or sham operated. Four weeks after OVX, they were assigned to 3 different groups to receive anti-RANKL monoclonal antibody (Ab alone (5 mg/kg single injection at 4 weeks after OVX, Ab group, teriparatide alone (80 μg/kg daily injection for 4 weeks from 4 weeks after OVX, PTH group, or mAb plus teriparatide (Ab + PTH group. Mice were sacrificed 8 weeks after OVX. Bone mineral density (BMD was measured at the femur and lumbar spine. Hind limbs were subjected to histological and histomorphometric analysis. Serum osteocalcin and CTX-I levels were measured to investigate the bone turnover. Compared with Ab group, Ab + PTH group showed a significant increase in BMD at distal femur and femoral shaft. Cortical bone volume was significantly increased in PTH and Ab + PTH groups compared with Ab group. Bone turnover in Ab + PTH group was suppressed to the same degree as in Ab group. The number of TRAP-positive multinucleated cells was markedly reduced in Ab and Ab + PTH groups. These results suggest that combined treatment of teriparatide with anti-RANKL antibody has additive effects on BMD in OVX mice compared with individual treatment.

  13. Correlated effects of selection for immunity in White Leghorn chicken lines on natural antibodies and specific antibody responses to KLH and M. butyricum

    Directory of Open Access Journals (Sweden)

    Gourichon David

    2008-01-01

    Full Text Available Abstract Background The effect of selection for three general immune response traits on primary antibody responses (Ab to Mycobacterium butyricum or keyhole limpet hemocyanin (KLH was studied in four experimental lines of White Leghorn chicken. Birds underwent 12 generations of selection for one of three different general immune criteria; high antibody response to Newcastle disease virus 3 weeks after vaccination (ND3, high cell-mediated immune response, using the wing web response to phytohemglutinin (PHA and high phagocytic activity, measured as carbone clearance (CC. Line ND3-L was selected on ND3, line PHA-L was selected on PHA, and line CC-L on CC, but all lines were measured for all three traits. The fourth line was a contemporary random bred control maintained throughout the selection experiment. Principal component analysis was used to distinguish clusters based on the overall set of immune measures. Results In the KLH immunised group, no differences were present between lines for natural antibodies binding to KLH and LPS, and, lines ND3-L and PHA-L had higher titers to LTA and anti-Gal titers measured before the immunisation protocol. The measure of ND3 was correlated positively with LPS titers measured post KLH immunisation and with the difference between LPS titers measured at day 0 and 7 post immunisation. In the M. butyricum immunised group, Line ND3-L showed significantly higher specific antibody response to M. butyricum, and this result agrees well with the hypothesis that the Th-1 pathway was expected to be selected for in this line. Conclusion This study has shown that the two different antigens KLH and M. butyricum gave rise to different responses in the set of selected lines, and that the response was only enhanced for the antigen associated with the same response mechanism as that for the trait (ND3, PHA or CC for which the line was selected. Interactions between innate and acquired immunity have been observed mainly for the

  14. Addressing drug effects on cut point determination for an anti-drug antibody assay.

    Science.gov (United States)

    Barbosa, Maria D F S; Gleason, Carol R; Phillips, Kelli R; Berisha, Flora; Stouffer, Bruce; Warrack, Bethanne M; Chen, Guodong

    2012-10-31

    The effect of trough levels of a monoclonal antibody drug (drugB) on screening cut point (CP) determination for an anti-drug antibody (ADA) assay was scrutinized and the conclusions substantiated by data from a phase 3 cancer clinical study. The ADA assay utilized an acid dissociation step and either 0 or 100 μg/ml drugB was added to the samples prior to obtaining the signals used for CP calculations. Serum samples from three different drug-naive populations were tested (healthy individuals, cancer patients enrolled in the drugB clinical trial and cancer patients whose serum samples were available commercially). For the same disease state samples, both the screening CP and confirmation CP were different when calculated during validation or from study sample analysis. It is reasonable to assume that variability was due to the patient heterogeneity, as they could have been at distinct stages of disease progression, and/or taking different medications, amongst other differences. The patients enrolled in the clinical trial were stratified as per protocol and hence represented a more homogeneous population. Drug effects on CP may be population dependent and also assay dependent. PMID:22750627

  15. Selenium and vitamin E effect on antibody production of sheep vaccinated against enzootic abortion (Chlamydia psittaci).

    Science.gov (United States)

    Giadinis, N; Koptopoulos, G; Roubles, N; Siarkou, V; Papasteriades, A

    2000-03-01

    The effect of selenium (Se) and vitamin E (vit E) on antibody production of sheep vaccinated against Chlamydia psittaci (ovis) was investigated. Thirty-two sheep, one year old, seronegative to Chlamydia infection, vaccinated against enterotoxemia and dewormed were used. Injectable sodium selenite (0.1 mg/kg b.w.) was given twice to animals of the first group (gSe), with a three week interval. The sheep of the second group (gE) received 1 g vit E each orally, six times at weekly intervals. The animals of the third group (gSeE) were given Se and vit E in doses and routes of administration as in gSe and gE. The animals of the fourth group served as controls (gC) and injected normal saline. The first vaccination was made at the time that the second Se injection was given. Revaccination was made two weeks later. The experiment lasted 29 weeks. The results indicated that Se alone led to a significant increase of Chlamydia antibody response (P < 0.05), but not when it was given in combination with vit E. Animals that received vit E (gE) had much lower titres, just above of those of the controls. PMID:10670702

  16. Effects of phenytoin on man's immunity. Evaluation of changes in serum immunoglobulins, complement, and antinuclear antibody.

    Science.gov (United States)

    Bardana, E J; Gabourel, J D; Davies, G H; Craig, S

    1983-02-01

    To determine the effects of phenytoin on serum immunoglobulins, complement, and antinuclear antibody conversion, a prospective, five-year longitudinal study was undertaken in 118 patients. Three major diagnostic groups were evaluated: 27 patients with idiopathic epilepsy, 50 with secondary epilepsy, and 41 with neuropathic syndromes without epilepsy. In addition, 83 normal volunteers were studied in a similar manner. Evaluations were performed prior to administration of phenytoin and at six-month intervals thereafter. Prior to treatment, patients with idiopathic epilepsy had a higher than expected incidence (13.5 percent, p less than 0.01) of low serum IgA (less than 61 mg/dl). Patients with secondary epilepsy and neuropathic disorders without epilepsy had a greater than expected incidence (9.2 percent, p less than 0.01; and 12 percent, p less than 0.01, respectively) of high serum IgA (greater than 417 mg/dl). Phenytoin treatment was associated with further decreases in serum IgA in patients with idiopathic epilepsy (p = 0.063) and secondary epilepsy (p = 0.008). Total serum IgE concentrations also decreased significantly in all patient categories during treatment with phenytoin. Minor decreases in serum IgG and IgM were noted, but serum IgD and complement remained unaffected. Antinuclear antibodies were observed with essentially the same frequency (10 percent) before and after phenytoin therapy. PMID:6600585

  17. Astatine-211: production, injection into monoclonal antibodies radiological effect, possible application to cancer treatment

    International Nuclear Information System (INIS)

    Methods developed in the Laboratory of Nuclear Problems, JINR, for producing astatine-211 and injecting it into monoclonal antibodies are described. The use of its diethylene triamine penta-acetic acid complex is shown to be the most effective method of injecting astatine into a biomolecules. The biological effect of the α-particles emitted from the astatine-211 is investigated using Chinese hamster fibroblasts and Ehrlich carcinoma cells. It is established that the mitotic activity depression, number of degenerating cells, number of cells with chromosome aberrations, and cellular surviving fraction depend on the concentration of the radionuclide in the medium 'in vitro'. The RBE of α-particles in comparison with 60Co γ-rays is 3. Injection of astatine-211 absorbed on tellurium particles into mice with ascitic tumors resulted in prolongation of their life or elimination of the tumors. (author). 39 refs, 7 figs

  18. Study on the Radioiodination of Sheep Anti-myeloma Polyclonal Antibodies for the Determination of in-vitro Cytotoxic Effect on Myeloma Cells

    International Nuclear Information System (INIS)

    The present work aims to study the effect of radiolabeled anti-myeloma polyclonal antibodies on the growth and viability of myeloma cells in-vitro. Two Sheep were immunized by myeloma cells (SP2/OR) as antigen. Productions of Sheep anti-myeloma polyclonal antibodies followed by radioiodination using different oxidizing agents were carried out. Labeled and unlabeled antibodies were incubated with myeloma cells. Growth and viability of myeloma cells were investigated before and after addition of antibodies. The results show significant reduction in growth and viability of myeloma cells by using labeled antibodies. This technique of treatment can be used in radio-immunotherapy of myeloma cell

  19. The allergy adjuvant effect of particles – genetic factors influence antibody and cytokine responses

    Directory of Open Access Journals (Sweden)

    Løvik Martinus

    2005-06-01

    Full Text Available Abstract Background There is increasing epidemiological and experimental evidence for an aggravating effect of particulate air pollution on asthma and allergic symptoms and, to a lesser extent, on allergic sensitization. Genetic factors appear to influence not only the magnitude, but also the quality of the adjuvant effect of particles with respect to allergen-specific IgE (Th2-associated and IgG2a (Th1-associated responses. In the present study, we aimed to investigate how the genetic background influences the responses to the allergen and particles alone and in combination. We examined how polystyrene particles (PSP affected the IgE and IgG2a responses against the model allergen ovalbumin (OVA, after subcutaneous injection into the footpad of BALB/cA, BALB/cJ, NIH and C3H/HeN mice, Further, ex vivo IL-4, IFN-γ and IL-10 cytokine secretion by Con A-stimulated cells from the draining popliteal lymph node (PLN five days after injection of OVA and PSP separately or in combination was determined. Results PSP injected with OVA increased the levels of OVA-specific IgE antibodies in all strains examined. In contrast, the IgG2a levels were significantly increased only in NIH and C3H/HeN mice. PSP in the presence of OVA increased cell numbers and IL-4, IL-10 and IFN-γ levels in BALB/cA, NIH and C3H/HeN mice, with the exception of IFN-γ in NIH mice. However, each mouse strain had their unique pattern of response to OVA+PSP, OVA and PSP, and also their unique background cytokine response (i.e. the cytokine response in cells from mice injected with buffer only. Conclusion Genetic factors (i.e. the strain of mice influenced the susceptibility to the adjuvant effect of PSP on both secondary antibody responses and primary cellular responses in the lymph node, as well as the cellular responses to both OVA and PSP given separately. Interestingly, PSP alone induced cytokine responses in the lymph node in some of the mouse strains. Furthermore, we found that

  20. Effects of Supplementation of Various Medium Components on Chinese Hamster Ovary Cell Cultures Producing Recombinant Antibody

    OpenAIRE

    Kim, Do Yun; Lee, Joon Chul; Chang, Ho Nam; Oh, Duk Jae

    2005-01-01

    Thirteen vitamins, twenty amino acids, hormones, inorganic salts, and other chemical agents, which constitute typical serum-free media, were evaluated for the development of fortified medium to enhance cell growth and productivity of recombinant antibody in the cultures of the recombinant Chinese hamster ovary (rCHO) cells. Two different rCHO cell lines, rCHO-A producing recombinant antibodies against the human platelet and rCHO-B secreting recombinant antibodies against the S surface antigen...

  1. Gold-coated graphene field-effect transistors for quantitative analysis of protein-antibody interactions

    Science.gov (United States)

    Tarasov, Alexey; Tsai, Meng-Yen; Flynn, Erin M.; Joiner, Corey A.; Taylor, Robert C.; Vogel, Eric M.

    2015-12-01

    Field-effect transistors (FETs) based on large-area graphene and other 2D materials can potentially be used as low-cost and flexible potentiometric biological sensors. However, there have been few attempts to use these devices for quantifying molecular interactions and to compare their performance to established sensor technology. Here, gold-coated graphene FETs are used to measure the binding affinity of a specific protein-antibody interaction. Having a gold surface gives access to well-known thiol chemistry for the self-assembly of linker molecules. The results are compared with potentiometric silicon-based extended-gate sensors and a surface plasmon resonance system. The estimated dissociation constants are in excellent agreement for all sensor types as long as the active surfaces are the same (gold). The role of the graphene transducer is to simply amplify surface potential changes caused by adsorption of molecules on the gold surface.

  2. Effects of in vitro asbestos exposure on natural killer and antibody-dependent cellular cytotoxicity

    International Nuclear Information System (INIS)

    Human peripheral blood lymphocytes (PBL) were exposed in vitro to asbestos fibers. Antibody-dependent cellular cytotoxicity (ADCC) activity and natural killer (NK) activity were examined by a chromium-51 release assay. There was a statistically significant enhancement of ADCC and NK activity by chrysotile and crocidolite fibers when cultured together with PBL for a period of 42 hr in medium containing a concentration of at least 2.5% fetal calf serum. Isolation of large granular lymphocytes to measure NK activity, however, showed the opposite effect when exposed to asbestos fibers. Their results indicated that asbestos fibers can directly affect lymphoid cytotoxic responses in vitro and may provide clues to immunopathogenic mechanisms for the occurrence of neoplasms in vivo

  3. Effect of antibody modifications on its biomolecular binding as determined by surface plasmon resonance.

    Science.gov (United States)

    Vashist, Sandeep Kumar

    2012-02-01

    A surface plasmon resonance (SPR)-based procedure was developed to determine the effect of antibody modifications on its biomolecular binding behavior. Mouse immunoglobulin G (IgG) was immobilized on a protein A-functionalized gold-coated SPR chip. Goat anti-mouse IgG and its various commercially available modifications (i.e., conjugated with atto 550, atto 647, tetramethylrhodamine isothiocyanate [TRITC], horseradish peroxidase [HRP], or biotin) were employed in exactly the same concentration for the detection of mouse IgG. The various modifications of goat anti-mouse IgG decreased its biomolecular binding to mouse IgG in the order of unmodified>HRP-labeled>atto 550-labeled>biotinylated>TRITC-labeled>atto 647-labeled. PMID:22093612

  4. Control of fibrotic changes through the synergistic effects of anti-fibronectin antibody and an RGDS-tagged form of the same antibody.

    Science.gov (United States)

    Tiwari, Anil; Kumar, Rajendra; Ram, Jagat; Sharma, Maryada; Luthra-Guptasarma, Manni

    2016-01-01

    TGF-β and myofibroblasts play a key role in fibrosis, characterized by aberrant synthesis and deposition of extracellular matrix (ECM) proteins, such as fibronectin (Fn) and collagen type I. There are two major roles played by integrins in the fibrotic pathology: (i) Fn-integrin interaction, coupled with cytokines like TGF-β, facilitates the self-polymerization of Fn and regulates cell-matrix fibrillar adhesions, thereby promoting fibrillogenesis; (ii) Integrin interaction with an RGD (arginine-glycine-aspartic) consensus sequence in the latent TGF-β, resulting in its activation. This study describes an anti-fibrotic strategy using a combination of two antibodies: Fn52 (targeted against the N-terminal 30 kDa region of fibronectin, a major site for Fn self-association), and its engineered form, Fn52RGDS (which binds to integrins). Interestingly, a synergistic effect of the cocktail in causing a decline in fibrotic features was confirmed in the context of fibrotic posterior capsular opacification (PCO), mediated by the lens epithelial cells (left behind after cataract surgery). Inclusion of Fn52RGDS to Fn52 aids in better diffusion of the antibodies; such combination therapies could be useful in the context of pathologies involving extensive remodeling of the fibronectin matrix, where the thick ECM offers a major challenge for efficient drug delivery. PMID:27484779

  5. The Effect of CD3-Specific Monoclonal Antibody on Treating Experimental Autoimmune Myasthenia Gravis

    Institute of Scientific and Technical Information of China (English)

    Ruonan Xu; Jianan Wang; Guojiang Chen; Gencheng Han; Renxi Wang; Beffen Shen; Yan Li

    2005-01-01

    CD3-specific monoclonal antibody was the first one used for clinical practice in field of transplantation. Recently,renewed interests have elicited in its capacity to prevent autoimmune diabetes by inducing immune tolerance. In this study, we tested whether this antibody can also be used to treat another kind of autoimmune disease myasthenia gravis (MG) and explored the possible mechanisms. MG is caused by an autoimmune damage mediated by antibody- and complement-mediated destruction of AChR at the neuromuscular junction. We found that administration of CD3-specific antibody (Fab)2 to an animal model with experimental autoimmune myasthenia gravis (EAMG) (B6 mice received 3 times of AChR/CFA immunization) could not significantly improve the clinical signs and clinical score. When the possible mechanisms were tested, we found that CD3 antibody treatment slightly down-regulated the T-cell response to AChR, modestly up-regulation the muscle strength. And no significant difference in the titers of IgG2b was found between CD3 antibody treated and control groups. These data indicated that CD3-specific antibody was not suitable for treating MG, an antibody- and complementmediated autoimmune disease, after this disease has been established. The role of CD3-specific antibody in treating this kind of disease remains to be determined.

  6. Evaluating the synergistic neutralizing effect of anti-botulinum oligoclonal antibody preparations.

    Directory of Open Access Journals (Sweden)

    Eran Diamant

    Full Text Available Botulinum neurotoxins (BoNT are considered some of the most lethal known substances. There are seven botulinum serotypes, of which types A, B and E cause most human botulism cases. Anti-botulinum polyclonal antibodies (PAbs are currently used for both detection and treatment of the disease. However, significant improvements in immunoassay specificity and treatment safety may be made using monoclonal antibodies (MAbs. In this study, we present an approach for the simultaneous generation of highly specific and neutralizing MAbs against botulinum serotypes A, B, and E in a single process. The approach relies on immunization of mice with a trivalent mixture of recombinant C-terminal fragment (Hc of each of the three neurotoxins, followed by a parallel differential robotic hybridoma screening. This strategy enabled the cloning of seven to nine MAbs against each serotype. The majority of the MAbs possessed higher anti-botulinum ELISA titers than anti-botulinum PAbs and had up to five orders of magnitude greater specificity. When tested for their potency in mice, neutralizing MAbs were obtained for all three serotypes and protected against toxin doses of 10 MsLD50-500 MsLD50. A strong synergistic effect of up to 400-fold enhancement in the neutralizing activity was observed when serotype-specific MAbs were combined. Furthermore, the highly protective oligoclonal combinations were as potent as a horse-derived PAb pharmaceutical preparation. Interestingly, MAbs that failed to demonstrate individual neutralizing activity were observed to make a significant contribution to the synergistic effect in the oligoclonal preparation. Together, the trivalent immunization strategy and differential screening approach enabled us to generate highly specific MAbs against each of the A, B, and E BoNTs. These new MAbs may possess diagnostic and therapeutic potential.

  7. Specific ion and buffer effects on protein-protein interactions of a monoclonal antibody.

    Science.gov (United States)

    Roberts, D; Keeling, R; Tracka, M; van der Walle, C F; Uddin, S; Warwicker, J; Curtis, R

    2015-01-01

    Better predictive ability of salt and buffer effects on protein-protein interactions requires separating out contributions due to ionic screening, protein charge neutralization by ion binding, and salting-in(out) behavior. We have carried out a systematic study by measuring protein-protein interactions for a monoclonal antibody over an ionic strength range of 25 to 525 mM at 4 pH values (5, 6.5, 8, and 9) in solutions containing sodium chloride, calcium chloride, sodium sulfate, or sodium thiocyante. The salt ions are chosen so as to represent a range of affinities for protein charged and noncharged groups. The results are compared to effects of various buffers including acetate, citrate, phosphate, histidine, succinate, or tris. In low ionic strength solutions, anion binding affinity is reflected by the ability to reduce protein-protein repulsion, which follows the order thiocyanate > sulfate > chloride. The sulfate specific effect is screened at the same ionic strength required to screen the pH dependence of protein-protein interactions indicating sulfate binding only neutralizes protein charged groups. Thiocyanate specific effects occur over a larger ionic strength range reflecting adsorption to charged and noncharged regions of the protein. The latter leads to salting-in behavior and, at low pH, a nonmonotonic interaction profile with respect to sodium thiocyanate concentration. The effects of thiocyanate can not be rationalized in terms of only neutralizing double layer forces indicating the presence of an additional short-ranged protein-protein attraction at moderate ionic strength. Conversely, buffer specific effects can be explained through a charge neutralization mechanism, where buffers with greater valency are more effective at reducing double layer forces at low pH. Citrate binding at pH 6.5 leads to protein charge inversion and the formation of attractive electrostatic interactions. Throughout the report, we highlight similarities in the measured

  8. Maternal antibodies in a wild altricial bird: effects on offspring immunity, growth and survival.

    Science.gov (United States)

    Pihlaja, Marjo; Siitari, Heli; Alatalo, Rauno V

    2006-09-01

    1. In many animals immunity is not fully developed until adulthood but the young still need protection against various sets of pathogens. Thus, bird nestlings are highly dependent on antibodies received from their mother (in the eggs) during their rapid early growth period. The relationship between maternal immunity and the development of neonates' own immunity has been poorly studied. 2. It has been suggested that immune function plays an important part in mediating resource competition between different life-history traits, e.g. growth and reproduction. Maternal investment of antibodies has potentially permanent effects on offspring phenotype. Thus, the trade-offs between the immune function and other important life-history traits in the offspring will also affect the fitness of the mother. 3. Our supplemental feeding experiment in the magpie Pica pica indicates that the immunoglobulin levels of offspring at hatching are dependent on a mother's nutritional condition. In addition, the amount of maternal immunoglobulins transferred to offspring increases along the laying order within a nest. 4. We also found that at the age of 8-10 days the immunoglobulin production of the offspring has already begun. Furthermore, the maternal immunoglobulin levels of the offspring at hatching were positively related to their immunoglobulin levels on day 10. 5. Maternal immunoglobulins did not significantly affect offspring growth, but there was a negative relationship between self-produced immunoglobulins and growth over the first 10 days, indicating a trade-off between these traits. Nestlings' weight, however, had a positive relationship with immunoglobulin production suggesting that the observed trade-off between growth and immunoglobulin production is due to catch-up growth of nestlings with a low hatching weight. We found that within nests nestlings with higher maternal antibody levels had higher survival rate until day 20, but between nests there was an opposite relationship

  9. Effects of Monoclonal Antibody Cetuximab on Proliferation of Non-small Cell Lung Cancer Cell lines

    Directory of Open Access Journals (Sweden)

    Zhen CHEN

    2010-08-01

    Full Text Available Background and objective The epidermal growth factor receptor (EGFR monoclonal antibody cetuximab has been used widely in non-small cell lung cancer patients. The aim of this study is to explore the effect of lung cancer cells (A549, H460, H1299, SPC-A-1 which were treated by cetuximab in vitro. Methods We studied the effects of increasing concentrations of cetuximab (1 nmol/L-625 nmol/L in four human lung cancer cell lines (A549, SPC-A-1, H460, H1229. CCK8 measured the inhibition of cell proliferation in each group. A549, SPC-A-1 were marked by PI and the statuses of apoptosis were observed. Western blot were used to detect the proliferation-related signaling protein and apoptosis-related protein in A549. Results The treatment with cetuximab resulted in the effect on cell proliferation and apoptosis in a time- and dosedependent manner. The expression of activated key enzymes (p-AKT, p-EGFR, p-MAPK in EGFR signaling transduction pathway were down-regulated more obviously. Conclusion Cetuximab is an effective targeted drug in the treatment of lung cancer cell lines, tissues, most likely to contribute to the inhibition of key enzymes in EGFR signaling transduction pathway.

  10. Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection.

    Science.gov (United States)

    Lynch, Rebecca M; Boritz, Eli; Coates, Emily E; DeZure, Adam; Madden, Patrick; Costner, Pamela; Enama, Mary E; Plummer, Sarah; Holman, Lasonji; Hendel, Cynthia S; Gordon, Ingelise; Casazza, Joseph; Conan-Cibotti, Michelle; Migueles, Stephen A; Tressler, Randall; Bailer, Robert T; McDermott, Adrian; Narpala, Sandeep; O'Dell, Sijy; Wolf, Gideon; Lifson, Jeffrey D; Freemire, Brandie A; Gorelick, Robert J; Pandey, Janardan P; Mohan, Sarumathi; Chomont, Nicolas; Fromentin, Remi; Chun, Tae-Wook; Fauci, Anthony S; Schwartz, Richard M; Koup, Richard A; Douek, Daniel C; Hu, Zonghui; Capparelli, Edmund; Graham, Barney S; Mascola, John R; Ledgerwood, Julie E

    2015-12-23

    Passive immunization with HIV-1-neutralizing monoclonal antibodies (mAbs) is being considered for prevention and treatment of HIV-1 infection. As therapeutic agents, mAbs could be used to suppress active virus replication, maintain suppression induced by antiretroviral therapy (ART), and/or decrease the size of the persistent virus reservoir. We assessed the impact of VRC01, a potent human mAb targeting the HIV-1 CD4 binding site, on ART-treated and untreated HIV-1-infected subjects. Among six ART-treated individuals with undetectable plasma viremia, two infusions of VRC01 did not reduce the peripheral blood cell-associated virus reservoir measured 4 weeks after the second infusion. In contrast, six of eight ART-untreated, viremic subjects infused with a single dose of VRC01 experienced a 1.1 to 1.8 log10 reduction in plasma viremia. The two subjects with minimal responses to VRC01 were found to have predominantly VRC01-resistant virus before treatment. Notably, two subjects with plasma virus load <1000 copies/ml demonstrated virus suppression to undetectable levels for over 20 days until VRC01 levels declined. Among the remaining four subjects with baseline virus loads between 3000 and 30,000 copies, viremia was only partially suppressed by mAb infusion, and we observed strong selection pressure for the outgrowth of less neutralization-sensitive viruses. In summary, a single infusion of mAb VRC01 significantly decreased plasma viremia and preferentially suppressed neutralization-sensitive virus strains. These data demonstrate the virological effect of this neutralizing antibody and highlight the need for combination strategies to maintain virus suppression. PMID:26702094

  11. Effect of anti-interleukin 2 monoclonal antibody treatment on the survival of rat cardiac allograft

    International Nuclear Information System (INIS)

    The effect of anti-interleukin 2 monoclonal antibody (anti-IL2 MoAb) and the accumulation of intravenously administered 125I-labeled anti-IL2 MoAb were examined in heterotopic rat cardiac allografts. Mouse anti-human recombinant IL2 MoAb was obtained by the hybridoma technique. The anti-IL2 MoAb, termed 8H-10, was an IgG2a which inhibited IL2-driven [3H]TdR incorporation in cytolytic T lymphocyte line cells at a dilution of 2(6). 8H-10 was injected iv at a dose of 200 micrograms/day for 8 consecutive days, beginning on the day of transplantation. Hearts from F344 rats (RT11v1) were transplanted into ACI recipient rats (RT1av1). The mean survival time was 7.6 +/- 0.8 days in untreated controls, 9.0 +/- 1.2 days in additional controls treated with mouse anti-sheep red blood cell monoclonal antibody, and 25.3 +/- 18.4 days in the anti-IL2 MoAb (8H-10)-treated group (P less than 0.05). Furthermore, the accumulation of intravenously administered 125I-labeled anti-IL2 MoAb (8H-10) was specifically seen in the grafted heart. In conclusion, these results suggest that IL2 may play an important role in allograft rejection and that anti-IL2 MoAb may serve as a useful immunosuppressive agent in clinical transplantation

  12. Effects of Cytokine IL-18 Gene on Antibody Production Induced by Ag85A DNA Vaccine

    Institute of Scientific and Technical Information of China (English)

    CHENHai-wen; WANGZi-ming; FANXiong-lin; GANWei-min; SHITao; XUZhi-kai; LIYuan

    2004-01-01

    Objective: To investigate the effects of plasmid containing human IL-18 gene on the humoral immune response of mice immunized by Ag85A DNA vaccines of Mycobacterium tuberculosis H37 Rv strain. Methods: Human IL-18 cDNA was amplified from RNA of peripheral blood mononuclear cells(PBMCs)by RT-PCR and cloned into the pGEM-TEasy vector.After sequencing IL-18 gene was subcloned into the the sites of BamH I and EooR I digestion of pcDNA3.1. BALB/c mice were injected intramuscularly with eukaryotic expression plasmid pclL18, together with MTB pcAg85A DNA vaccines. The same immunization was repeated three times at intervals of two weeks. Mouse serawere collected at two weeks after the each injection. The titers of anti-Ag85A antibody were detected by ELISA. Results:IL-18 cDNA was amplified successfully from RNA of human PBMCs by RT-PCR and the result of sequencing was correct. The IL-18 gene was correctly inserted into the vector pcDNA3.1, which was confirmed with BamH I and EooR I digestion analysis. The positive plasmid was called pcIL18.After being immtmized with DNA vaccines,the titers of antibody obtained from mice being immtmized by pcAg85A combining with pclL18 were superior to mice inmunized by pcAg85A independently. Conc/us/on: Combination of IL-18 gene with MTB pcAg85A DNA vaccine could observably enhance the humoral immune responses to pcAg85A. It remains further investigated whether IL-18 gene plus MTB pcAg85A DNA vaccine could markedly induce the cellular mediated immune response to Ag85A or not.

  13. The strong in vivo anti-tumor effect of the UIC2 monoclonal antibody is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity.

    Directory of Open Access Journals (Sweden)

    Gábor Szalóki

    Full Text Available P-glycoprotein (Pgp extrudes a large variety of chemotherapeutic drugs from the cells, causing multidrug resistance (MDR. The UIC2 monoclonal antibody recognizes human Pgp and inhibits its drug transport activity. However, this inhibition is partial, since UIC2 binds only to 10-40% of cell surface Pgps, while the rest becomes accessible to this antibody only in the presence of certain substrates or modulators (e.g. cyclosporine A (CsA. The combined addition of UIC2 and 10 times lower concentrations of CsA than what is necessary for Pgp inhibition when the modulator is applied alone, decreased the EC50 of doxorubicin (DOX in KB-V1 (Pgp+ cells in vitro almost to the level of KB-3-1 (Pgp- cells. At the same time, UIC2 alone did not affect the EC50 value of DOX significantly. In xenotransplanted severe combined immunodeficient (SCID mice co-treated with DOX, UIC2 and CsA, the average weight of Pgp+ tumors was only ∼10% of the untreated control and in 52% of these animals we could not detect tumors at all, while DOX treatment alone did not decrease the weight of Pgp+ tumors. These data were confirmed by visualizing the tumors in vivo by positron emission tomography (PET based on their increased 18FDG accumulation. Unexpectedly, UIC2+DOX treatment also decreased the size of tumors compared to the DOX only treated animals, as opposed to the results of our in vitro cytotoxicity assays, suggesting that immunological factors are also involved in the antitumor effect of in vivo UIC2 treatment. Since UIC2 binding itself did not affect the viability of Pgp expressing cells, but it triggered in vitro cell killing by peripheral blood mononuclear cells (PBMCs, it is concluded that the impressive in vivo anti-tumor effect of the DOX-UIC2-CsA treatment is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity (ADCC.

  14. The strong in vivo anti-tumor effect of the UIC2 monoclonal antibody is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity.

    Science.gov (United States)

    Szalóki, Gábor; Krasznai, Zoárd T; Tóth, Ágnes; Vízkeleti, Laura; Szöllősi, Attila G; Trencsényi, György; Lajtos, Imre; Juhász, István; Krasznai, Zoltán; Márián, Teréz; Balázs, Margit; Szabó, Gábor; Goda, Katalin

    2014-01-01

    P-glycoprotein (Pgp) extrudes a large variety of chemotherapeutic drugs from the cells, causing multidrug resistance (MDR). The UIC2 monoclonal antibody recognizes human Pgp and inhibits its drug transport activity. However, this inhibition is partial, since UIC2 binds only to 10-40% of cell surface Pgps, while the rest becomes accessible to this antibody only in the presence of certain substrates or modulators (e.g. cyclosporine A (CsA)). The combined addition of UIC2 and 10 times lower concentrations of CsA than what is necessary for Pgp inhibition when the modulator is applied alone, decreased the EC50 of doxorubicin (DOX) in KB-V1 (Pgp+) cells in vitro almost to the level of KB-3-1 (Pgp-) cells. At the same time, UIC2 alone did not affect the EC50 value of DOX significantly. In xenotransplanted severe combined immunodeficient (SCID) mice co-treated with DOX, UIC2 and CsA, the average weight of Pgp+ tumors was only ∼10% of the untreated control and in 52% of these animals we could not detect tumors at all, while DOX treatment alone did not decrease the weight of Pgp+ tumors. These data were confirmed by visualizing the tumors in vivo by positron emission tomography (PET) based on their increased 18FDG accumulation. Unexpectedly, UIC2+DOX treatment also decreased the size of tumors compared to the DOX only treated animals, as opposed to the results of our in vitro cytotoxicity assays, suggesting that immunological factors are also involved in the antitumor effect of in vivo UIC2 treatment. Since UIC2 binding itself did not affect the viability of Pgp expressing cells, but it triggered in vitro cell killing by peripheral blood mononuclear cells (PBMCs), it is concluded that the impressive in vivo anti-tumor effect of the DOX-UIC2-CsA treatment is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity (ADCC). PMID:25238617

  15. Filarial-specific antibody response in East African bancroftian filariasis: effects of host infection, clinical disease, and filarial endemicity

    DEFF Research Database (Denmark)

    Jaoko, Walter G; Simonsen, Paul E; Meyrowitsch, Dan W;

    2006-01-01

    The effect of host infection, chronic clinical disease, and transmission intensity on the patterns of specific antibody responses in Bancroftian filariasis was assessed by analyzing specific IgG1, IgG2, IgG3, IgG4, and IgE profiles among adults from two communities with high and low Wuchereria...... bancrofti endemicity. In the high endemicity community, intensities of the measured antibodies were significantly associated with infection status. IgG1, IgG2, and IgE were negatively associated with microfilaria (MF) status, IgG3 was negatively associated with circulating filarial antigen (CFA) status...

  16. Effect of using heat-inactivated serum with the Abbott human T-cell lymphotropic virus type III antibody test.

    OpenAIRE

    Jungkind, D. L.; DiRenzo, S A; Young, S J

    1986-01-01

    The Abbott enzyme immunoassay (Abbott Laboratories, North Chicago, Ill.) for human T-cell lymphotropic virus type III (HTLV-III) antibody was evaluated to determine the effect of using heat-inactivated (56 degrees C for 30 min) serum as the sample. Each of 58 nonreactive serum samples gave a higher A492 value when tested after heat inactivation. Ten of the samples became reactive after heating. Heat-inactivated serum should not be used in the current Abbott HTLV-III antibody test, because thi...

  17. PROTECTIVE EFFECT OF CUTANEOUS ANTIBODY PRODUCED BY CHANNEL CATFISH IMMUNE TO ICHTHYOPHTHIRIUS ON COHABITED NON-IMMUNE CATFISH

    Science.gov (United States)

    Fish recovered from sublethal ichthyophthiriasis acquire protective immunity against Ichthyophthirius (Ich). This study evaluated the protective effect of cutaneous antibody excreted by channel catfish immune to Ich on cohabited non-immune catfish. Non-immune and immune fish controls were separatel...

  18. Effect of levothyroxine on live birth rate in euthyroid women with recurrent miscarriage and TPO antibodies (T4-LIFE study)

    DEFF Research Database (Denmark)

    Vissenberg, R; van Dijk, M M; Fliers, E;

    2015-01-01

    BACKGROUND: Thyroid peroxidase antibodies (TPO-Ab) in euthyroid women are associated with recurrent miscarriage (RM) and other pregnancy complications such as preterm birth. It is unclear if treatment with levothyroxine improves pregnancy outcome. Aim To determine the effect of levothyroxine admi...

  19. The Effectiveness of Implementing an E-Book: Antigen and Antibody Reaction for Diagnosis of Diseases in Microbiology Learning

    Science.gov (United States)

    Samrejrongroj, Phakakrong; Boonsiri, Tanit; Thunyaharn, Sudaluck; Sangarun, Preeyapan

    2014-01-01

    Currently very few Thai Immunology e-Books are available online. The authors created an online e-Book titled, "Antigen and Antibody Reaction for Diagnosis of Diseases" and used a quasi experimental research design to assess the effectiveness of its implementation in terms of knowledge gained, written exam scores and student satisfaction.…

  20. Radiolabeled antibodies in prostate cancer: A case study showing the effect of host immunity on antibody bio-distribution

    International Nuclear Information System (INIS)

    Objectives: Human tumors xenografted in immunodeficient mice are crucial models in nuclear medicine to evaluate the effectiveness of candidate diagnostic and therapeutic compounds. However, little attention has been focused on the biological profile of the host model and its potential effects on the bio-distribution and tumor targeting of the tracer compound under study. We specifically investigated the dissimilarity in bio-distribution of 111In-DTPA-5A10, which targets free prostate specific antigen (fPSA), in two animal models. Methods: In vivo bio-distribution studies of 111In-DTPA-5A10 were performed in immunodeficient BALB/c-nu or NMRI-nu mice with subcutaneous (s.c.) LNCaP tumors. Targeting-specificity of the tracer was assessed by quantifying the uptake in (a) mice with s.c. xenografts of PSA-negative DU145 cells as well as (b) BALB/c-nu or NMRI-nu mice co-injected with an excess of non-labeled 5A10. Finally, the effect of neonatal Fc-receptor (FcRn) inhibition on the bio-distribution of the conjugate was studied by saturating FcRn-binding capacity with nonspecific IgG1. Results: The inherent biological attributes of the mouse model substantially influenced the bio-distribution and pharmacokinetics of 111In-DTPA-5A10. With LNCaP xenografts in BALB/c-nu mice (with intact B and NK cells but with deficient T cells) versus NMRI-nu mice (with intact B cells, increased NK cells and absent T cells), we observed a significantly higher hepatic accumulation (26 ± 3.9 versus 3.5 ± 0.4%IA/g respectively), and concomitantly lower tumor uptake (25 ± 11 versus 52 ± 10%IA/g respectively) in BALB/c-nu mice. Inhibiting FcRn by administration of nonspecific IgG1 just prior to 111In-DTPA-5A10 did not change tumor accumulation significantly. Conclusions: We demonstrated that the choice of immunodeficient mouse model importantly influence the bio-distribution of 111In-DTPA-5A10. This study further highlighted important considerations in the evaluation of preclinical tracers

  1. INHIBITION OF Acinetobacter baumannii ADHESION BY ANTI-FIMBRIAL ANTIBODY: THE FIMBRIAL ANTIGEN EFFECTIVENESS

    Directory of Open Access Journals (Sweden)

    Hadeel K. Musafer

    2013-01-01

    Full Text Available Collecting samples of Acinetobacter baumannii taken from different clinical cases of wounds, septicemia, and urinary tract infections. That was accomplished by taking (296 samples from Baghdad educational hospital and Ibn-al-Baladi hospital. Samples were cultured on solid media (McConkey and blood agars, and according to microscopical, cultural, and biochemical identification, in addition to using API 20-E system, (21 isolates of A. baumannii were identified and in percentage of 47.619, 9.523, 14.285, and 28.571 for wound, blood, sputum, and urine samples, respectively. Methods: detection of fimbriated bacterial isolates among 21 isolates, and all those isolated were fimbriae forming isolates; isolate number (9 was selected as an effective isolate in formation of fimbriae. Non-forming fimbriae isolate of Shigella flexneri is used as negative control. Results and Conclusion: the average of adherence of fimbriated bacterial cell with human epithelial cells was reached (50 adherent bacterial cell per epithelial cell compared with the average of adherence of control isolate (12 adherent bacterial cell per epithelial cell, the inhibition processes are performed: Inhibition of bacterial adherence by specific antibodies of fimbriae antigen showed inhibition effect of adherence in respect to fimbriated isolate A. baumannii 9 also the subminimum inhibitory concentration for four antibiotics (Gentamicin, Tobramycin, Cefepime, and Amikacin inhibit the adherence of fimbriated isolate. The isolates (used in the study have the ability to agglutinate Saccharomyces cerevisiae and human red blood corpuscles (RBCs. The study of effect of different fimbriae extract concentrations (25, 50, 100 μg/ml on immune cells; consequently, reached to the following results: Concentrations of (25, 50, 100 μg/ml showed a negative effect on lymphocyte and PMNs viability which increased significantly (P≤0.05 with increasing of fimbriae extract concentration. On the other hand

  2. Antithyroid microsomal antibody

    Science.gov (United States)

    Thyroid antimicrosomal antibody; Antimicrosomal antibody; Microsomal antibody; Thyroid peroxidase antibody; TPOAb ... Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also been linked to an increased risk ...

  3. Effect of anti-carbohydrate antibodies on HIV infection in a monocytic cell line (U937)

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C; Clausen, H; Mathiesen, Lars Reinhardt; Nielsen, Jens Ole

    1991-01-01

    Monoclonal antibodies (mAbs) against carbohydrate epitopes of gp120 have recently been found to inhibit HIV infection of lymphocytes in vitro thereby opening new possibilities for vaccine considerations. Antibody-dependent enhancement of infection has however come increasingly into focus. This...... study therefore investigated the neutralization of HIV in a monocytic cell line (U937) using mAbs against these carbohydrate gp120-epitopes. While antibodies against one of the epitopes (AI) neutralized infection of U937 cells despite binding to the Fc-receptor, one mAb against the sialosyl-Tn epitope...

  4. The effects of acylation stimulating protein supplementation VS antibody neutralization on energy expenditure in wildtype mice

    Directory of Open Access Journals (Sweden)

    Gao Ying

    2010-04-01

    Full Text Available Abstract Background Acylation stimulating protein (ASP is an adipogenic hormone that stimulates triglyceride (TG synthesis and glucose transport in adipocytes. Previous studies have shown that ASP-deficient C3 knockout mice are hyperphagic yet lean, as they display increased oxygen consumption and fatty acid oxidation compared to wildtype mice. In the present study, antibodies against ASP (Anti-ASP and human recombinant ASP (rASP were tested in vitro and in vivo. Continuous administration for 4 weeks via osmotic mini-pump of Anti-ASP or rASP was evaluated in wildtype mice on a high-fat diet (HFD to examine their effects on body weight, food intake and energy expenditure. Results In mature murine adipocytes, rASP significantly stimulated fatty acid uptake (+243% vs PBS, P Conclusion In vitro, Anti-ASP effectively neutralized ASP stimulated fatty acid uptake. In vivo, Anti-ASP treatment increased whole body energy utilization while rASP increased energy storage. Therefore, ASP is a potent anabolic hormone that may also be a mediator of energy expenditure.

  5. [Effect of thalassemia panel reactive antibody on proliferation and apoptosis of cord blood CD34(+) cells].

    Science.gov (United States)

    Yang, Xing-Ge; Lu, Xue-Liang; Xu, Lü-Hong; Fang, Jian-Pei

    2012-02-01

    The study was purposed to explore the effect of panel reactive antibody (PRA) serum from patients with β-thalassemia on proliferation and apoptosis of the CD34(+)cells from cord blood and its mechanism. CD34(+) cells of umbilical cord blood were incubated with different sera and complement respectively. After incubation, the samples were centrifuged and the supernatants were collected for lactate dehydrogenase (LDH) detection, and the CD34(+) cells were harvested and measured for the apoptosis by flow cytometry with Annexin V/PI. The intracellular DNA synthesis were also quantified by [(3)H]TdR incorporation using liquid scintillation counter. The results showed that concentration of LDH in PRA positive groups was higher as compared with control group, and the DNA synthesis of CD34(+) cells in PRA positive groups were inhibited. There were no differences in the percentage of cell apoptosis and necrosis among different groups. It is concluded that thalassemic serum PRA impairs the cell membrane, inhibits the DNA synthesis, which can be increased by addition of the complement, but PRA had no significant effect on apoptosis of CD34(+) cells. PMID:22391181

  6. Effects of anti-tumor necrosis factor-alpha and anti-intercellular adhesion molecule-1 antibodies on ischemia/reperfusion lung injury.

    Science.gov (United States)

    Chiang, Chi-Huei

    2006-10-31

    Inhibition of neutrophil activation and adherence to endothelium by antibodies to tumor necrosis factor-alpha (TNF-alpha) and intercellular adhesion molecules (ICAM-1), respectively, might attenuate ischemia-reperfusion injury (I/R). I/R was conducted in an isolated rat lung model. Anti-TNF-alpha antibody and/or anti-ICAM-1 antibody were added before ischemia or after reperfusion. Hemodynamic changes, lung weight gain (LWG), capillary filtration coefficients (Kfc), and pathologic changes were assessed to evaluate the severity of I/R. The LWG, Kfc, pathological changes and lung injury score of treatment groups with anti-TNF-alpha antibody treatment, either pre-ischemia or during reperfusion, were less than those observed in control groups. Similar findings were found in group treated with anti-ICAM-1 antibody or combination therapy during reperfusion. In contrast, pre-I/R treatment with anti-ICAM-1 antibody induced severe lung edema and failure to complete the experimental procedure. No additional therapeutic effect was found in combination therapy. We conclude that TNF-alpha and ICAM-1 play important roles in I/R. Anti-TNF-alpha antibody has therapeutic and preventive effects on I/R. However, combined therapy with anti-TNF-alpha antibody and anti-ICAM-1 antibody may have no additive effect and need further investigation. PMID:17294835

  7. A conserved multi-gene family induces cross-reactive antibodies effective in defense against Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Subhash Singh

    Full Text Available BACKGROUND: Two related merozoite surface proteins, MSP3 and MSP6, have previously been identified as targets of antibody-dependent cellular inhibition (ADCI, a protective mechanism against Plasmodium falciparum malaria. Both MSP3 and MSP6 share a common characteristic small N-terminal signature amino-acid stretch (NLRNA/G, a feature similar to MSP3-like orthologs identified in other human and primate malaria parasites. METHODS/RESULTS: This signature amino-acid sequence led to the identification of eight ORFs contiguously located on P. falciparum chromosome 10. Our subsequent investigations on their expression, localization, sequence conservation, epitope sharing, immunogenicity and the functional role of antibodies in defense are reported here. Six members of P. falciparum MSP3-multigene family share similar sequence organization within their C-terminal regions, are simultaneously expressed as merozoite surface proteins and are highly conserved among parasite isolates. Each of these proteins is a target of naturally occurring antibodies effective at parasite killing in ADCI assays. Moreover, both naturally occurring antibodies and those generated by immunization display cross-reactivity with other members of the family and exhibit varied binding avidities. CONCLUSIONS/SIGNIFICANCE: The unusual characteristics of the MSP3 multi-gene family lead us to hypothesize that the simultaneous expression of targets eliciting cross-reactive antibody responses capable of controlling parasite densities could represent an immune process selected through evolution to maintain homeostasis between P. falciparum and human hosts; a process that allows the continuous transmission of the parasite without killing the host. Our observations also have practical consequences for vaccine development by suggesting MSP3 vaccine efficacy might be improved when combined with the various C-terminus regions of the MSP3 family members to generate a wider range of antibodies

  8. Effects of Anti-Mosquito Salivary Glands and Deglycosylated Midgut Antibodies of Anopheles stephensi on Fecundity and Longevity

    Directory of Open Access Journals (Sweden)

    H Mohammadzadeh Hajipirloo

    2005-09-01

    Full Text Available With the aim of controlling malaria by reducing vector population, the effects of antibodies produced against salivary glands and deglycosylated midgut antigens of Anopheles stephensi mosquitoes on fecundity and longevity of the same species were tested. Three deglycosylated preparations of midgut and two preparations of salivary glands were produced, conjugated with aluminum hydroxide gel, and subcutaneously injected to shoulders of TO (Turner Out-bred mice. After 4 immunizations and assurance of enough antibody production against utilized antigenic suspensions, effects of blood feeding on immunized and control mice were assayed. Insoluble preparation of midgut showed the strongest effect with 23.5% reduction in egg laying, and increasing death rate of vectors in third day after feeding. No significant reduction in fecundity or survivorship was seen with other preparations. Anopheles midgut insoluble antigens are potential candidates for designing vaccines against malaria vectors and further investigations need to be done to find effective antigens and the best way of their use.

  9. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    Yeast surface display is an effective tool for antibody affinity maturation because yeast can be used as an all-in-one workhorse to assemble, display and screen diversified antibody libraries. By employing the natural ability of yeast Saccharomyces cerevisiae to efficiently recombine multiple DNA...

  10. Effect of chelating agents on the distribution of monoclonal antibodies in mice

    International Nuclear Information System (INIS)

    The potential for altering the biodistribution of radiolabel from gallium- and indium-labeled mouse monoclonal antibodies was investigated in mice using metal chelating agents. The chelating agents used were desferrioxamine (DFO), diethylenetriaminepentaacetic acid (DTPA), ethylenediamine-di (O-hydroxyphenylacetic acid) (EDHPA), and 2,2' dipyridyl (DIPY). The mouse monoclonal antibody LICR-LON-M8 was labeled with 111In after conjugation to DTPA, and with 67Ga after conjugation to DFO. All the chelating agents except DIPY altered the biodistribution of [67Ga]citrate and [111In]citrate but did not affect the 48-hr tissue uptake of label from [111In]DTPA-M8 or [67Ga]DFO-M8, confirming the in vivo stability of the antibody conjugates. Label fixed in the tissues was inaccessible to the chelating agents, indicating that they will not be suitable for reducing the high background liver radioactivity in patients undergoing scanning with indium-labeled antibodies

  11. Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens

    DEFF Research Database (Denmark)

    Tweyongyere, Robert; Mawa, Patrice A.; Emojong, Nicholas O.;

    2009-01-01

    with those first treated after delivery (undetected (88.5%), light (10.6%), moderate (0.9%) and heavy (0%), p = 0.16). Parasite specific antibody levels were lower during pregnancy than after delivery. Praziquantel treatment during pregnancy boosted anti-worm IgG isotypes and to a lesser extent Ig......E, but these boosts were less pronounced than in women whose treatment was delayed until after delivery. Praziquantel had limited effects on antibodies against egg antigens. Conclusion S mansoni antigen-specific antibody levels and praziquantel-induced boosts in antibody levels were broadly suppressed...

  12. Differential effects of passive immunization with nicotine-specific antibodies on the acute and chronic distribution of nicotine to brain in rats.

    Science.gov (United States)

    Pentel, P R; Dufek, M B; Roiko, S A; Lesage, M G; Keyler, D E

    2006-05-01

    Vaccination against nicotine blocks or attenuates nicotine-related behaviors relevant to addiction in rats. Passive immunization with nicotine-specific antibodies is an alternative to vaccination with the potential advantages of allowing control of antibody dose and affinity. In the current study, the effects of two antibodies on the distribution of nicotine to brain were evaluated during chronic nicotine administration in rats; the monoclonal antibody Nic311 (K(d) = 60 nM) and nicotine-specific antiserum (K(d) = 1.6 nM). Nicotine was administered via repeated i.v. bolus doses over 2 days and antibody was administered during the first day. Neither antibody appreciably reduced the chronic accumulation of nicotine in brain, despite high protein binding of nicotine in serum (98.9%) and a 73% reduction in the unbound serum nicotine concentration with the highest Nic311 dose. However, both antibodies substantially reduced the early distribution of nicotine to brain 5 min after a dose. The higher affinity antibody was no more effective than Nic311. The highest Nic311 dose produced serum antibody levels 10 times higher than those reported with vaccination. The efficacy of Nic311 was dose-related, with the highest dose producing a 76% decrease in the early distribution of nicotine to brain. These findings, along with previous data, suggest that the primary effect of passive immunization is to slow, rather than prevent, the distribution of nicotine to brain. In the setting of chronic nicotine dosing, antibodies with a moderate affinity for nicotine produced substantial effects on the early distribution of nicotine to brain and were as effective as higher affinity antibodies. PMID:16407464

  13. Myelin protein zero and its antibody in serum as biomarkers of n-hexane-induced peripheral neuropathy and neurotoxicity effects

    Institute of Scientific and Technical Information of China (English)

    Jia Xiaowei; Liu Qingjun; Zhang Yanshu; Dai Yufei; Duan Huawei; Bin Ping; Niu Yong

    2014-01-01

    Background Chronic exposure to n-hexane can lead to peripheral neuropathy that no effective treatment regimen could be applied presently.This study investigated whether myelin protein zero (P0) protein and its antibody could be used to distinguish n-hexane intoxication and protect workers from peripheral neuropathy.Methods We compared P0 protein and its antibody among three levels of n-hexane-exposed groups,which included 18 patients with n-hexane-induced peripheral neuropathy as case group,120 n-hexane-exposed workers as n-hexaneexposed control group,and 147 non-hexane-exposed participants used as control group.ELISA method was applied to detect P0 protein and its antibody.Results P0 protein in serum was significantly higher in the case group and n-hexane-exposed control group in comparison with the control group (P<0.01).Compared with the n-hexane-exposed control group,the case group also had significant increase of P0 protein (P<0.01).After 6 months therapy,P0 protein was observed to decrease significantly in the case group (P<0.01).The P0 antibody in serum was significantly higher in the n-hexane-exposed control group than in the control group (P<0.01),but not significantly different between cases and controls.Conclusions P0 antibodies in serum may be a short-term effect biomarker for n-hexane exposure.P0 protein in serum may be an early effective biomarker for peripheral nerve neuropathy and its biological limit value needs investigation in the future study.

  14. Effective Binding of a Phosphatidylserine-Targeting Antibody to Ebola Virus Infected Cells and Purified Virions

    OpenAIRE

    Dowall, S. D.; Graham, V A; Corbin-Lickfett, K; C. Empig; Schlunegger, K.; Bruce, C B; Easterbrook, L.; Hewson, R.

    2015-01-01

    Ebola virus is responsible for causing severe hemorrhagic fevers, with case fatality rates of up to 90%. Currently, no antiviral or vaccine is licensed against Ebola virus. A phosphatidylserine-targeting antibody (PGN401, bavituximab) has previously been shown to have broad-spectrum antiviral activity. Here, we demonstrate that PGN401 specifically binds to Ebola virus and recognizes infected cells. Our study provides the first evidence of phosphatidylserine-targeting antibody reactivity again...

  15. Effect of nonprotective vaccination on antibody response to subsequent human immunodeficiency virus infection.

    OpenAIRE

    Pincus, S H; Messer, K G; Hu, S L

    1994-01-01

    We have investigated the systemic anti-HIV antibody response in chimpanzees who were immunized with live vaccinia containing either the HIV envelope glycoprotein (gp160IIIB) or a control antigen (herpes simplex virus glycoprotein D) and then challenged with either a high dose (300,000 TCID50) or low dose (100 TCID50) of HIVIIIB. HIV was subsequently isolated from all animals, indicating failure of the vaccination to protect against HIV infection. Serum antibody responses were evaluated before...

  16. Excipient effects on humanized monoclonal antibody interactions with silicone oil emulsions.

    Science.gov (United States)

    Britt, Keith A; Schwartz, Daniel K; Wurth, Christine; Mahler, Hanns-Christian; Carpenter, John F; Randolph, Theodore W

    2012-12-01

    The interfacial adsorption of three humanized monoclonal antibodies to emulsions of microdroplets of silicone oil was examined using indirect measurement via integrated peak areas in size-exclusion high-performance liquid chromatograms. The level of silicone oil far exceeded the typical levels used in prefillable syringes. The three antibodies rapidly adsorbed to silicone oil-water interfaces in various buffer formulations. Addition of 140 mM NaCl to solutions buffered with 10 mM l-histidine, pH 6.0, increased the amount of protein adsorbed. Conversely, the extent of adsorption was significantly decreased by the addition of 0.03% (w/v) Tween® 20. Stern-Volmer constants determined from intrinsic tryptophan fluorescence quenching by acrylamide suggested that the tertiary structure of the adsorbed antibodies was significantly perturbed. However, no aggregation or precipitation of the antibodies was detected. Flow cytometric analysis of emulsions of fluorescently stained silicone oil in solutions containing fluorescently labeled antibodies and light microscopy experiments suggested that agglomeration of silicone oil droplets in the emulsions occurred. Zeta potentials measured for silicone oil microdroplets with adsorbed antibodies suggested that droplet agglomeration was probably the result of reduced electrostatic energy barriers to droplet collisions. PMID:22987313

  17. The effects of lupus and antiphospholipid antibody syndrome on foetal outcomes.

    Science.gov (United States)

    Nalli, C; Iodice, A; Andreoli, L; Lojacono, A; Motta, M; Fazzi, E; Tincani, A

    2014-05-01

    Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease that primarily affects women of childbearing-age. Antiphospholipid syndrome (APS) is a systemic autoimmune disorder defined by the occurrence of venous and arterial thrombosis, often multiple, and pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). Recently, the long-term outcome of children born to patients with lupus and APS has become a major topic of interest both to patients and physicians. One of the major problems related to maternal disease is preterm delivery with all the consequences that this condition may bring. Prematurity may also be due to the presence of aPL; however, aPL do not generally display any thrombotic potential on neonates. Another complication may be neonatal lupus (NL), mediated by the presence of maternal antibodies (anti-Ro/SSA and anti-La/SSB). In addition, behaviour and neuropsychological outcomes have also been a matter of interest, but there are currently few data available. Beyond the biological influence of both maternal disease and autoimmune background, it is important to focus on the possible influence of maternal chronic illness on the neuropsychological development of her children. Whether aPL exposure could have a direct effect on brain development is still being debated. In children of mothers with APS, language delays have been noted and learning disabilities were described with a higher rate than the general age-school population. Several studies were performed on children born to lupus mothers: even if maternal lupus does not seem to impair intelligence levels, it may increase the occurrence of learning disabilities and particularly dyslexia in male children. To the best of our knowledge, no studies are available on the long-term outcome of children born to mothers with lupus or APS and particularly regarding the development of autoimmune diseases. Nevertheless, common experience of experts in the field is that these children do

  18. EFFECT OF SELENIUM SUPPLEMENTATION ON ANTIBODY TITRES AGAINST INFECTIOUS BURSAL DISEASE VACCINE IN BROILER CHICKS

    Directory of Open Access Journals (Sweden)

    M. Arshad, M. Siddique, M. Ashraf and H. A. Khan

    2005-10-01

    Full Text Available A total of 200 chicks were raised upto 43 days of age under controlled experimental conditions. The birds were randomly divided into four groups A, B, C and D of 50 birds each at the age of day one. Birds of groups A and B were not supplemented with selenium, while those of groups C and D were given selenium @ 0.06 mg/Kg of feed from day one to day 43. The birds of groups B and D were vaccinated against infectious bursal disease (IBD at the age of day 10 and boosted at the age of day 25. The effect of selenium on humoral immune response was evaluated by recording weekly serum antibody titres against IBD through indirect haemagglutination (IHA test. The cumulative mean titres (CMT recorded in groups A, B, C and D were 15, 53, 16 and 61, respectively (P<0.05. These results indicate that selenium supplementation may help to increase post vaccination humoral immune response against IBD in broiler chicks.

  19. Effect of 60Co γ-rays on the lymphocyte subsets with monoclonal antibodies

    International Nuclear Information System (INIS)

    Three kinds of monoclonal antibodies (McAb), OkT4 McAb, OkT3 McAb and HI43, were used to identify T helper (Th). T suppresser (Ts) and B lymphocytes respectively. After lympbocytes were immediately exposed to 0.1 Gy, 0.25 Gy and 4 Gy 60Co γ-rays, 200 cells were counted to obtain the percentage of immunofluorescence positive cells. The results show that when the Th, Ts and B lymphocytes were irradiated by 0.1 Gy 60Co γ-rays, their abilities to combine with McAb decreased significantly. The radiation effect was more remarkable with increasing radiation dosage. Three kinds of the immunofluorescence positive cells percentages were analysed with weighted linear regression method. The relational coefficients (r) of Th, Ts and B lymphocytes were 0.8131, 0.8832 and 0.9086. The significant tests of regression coefficient showed that the radiosensitivities of Ts and B lymphocytes were higher than that of Th lymphocytes

  20. Effective prophylaxis against rotavirus diarrhea using a combination of Lactobacillus rhamnosus GG and antibodies

    Directory of Open Access Journals (Sweden)

    Hammarström Lennart

    2007-09-01

    Full Text Available Abstract Background Rotavirus is a worldwide cause of infectious infantile diarrhea that claims over 600,000 lives annually. Recently, two new vaccine candidates have been developed but their efficacy in developing countries, still remains to be proven. Oral delivery of specific immunoglobulins provides passive immunity and is a fast acting treatment for rotavirus diarrhea. Probiotic bacteria have also gained considerable attention lately as treatment for rotavirus diarrhea. Here we report an evaluation of the therapeutic potential of different probiotics and their combination with anti – rotavirus antibodies in a mouse model of rotavirus diarrhea. Results Of the six probiotic bacteria tested, Lactobacillus rhamnosus strain GG had the strongest influence in reducing prevalence, duration and severity of diarrhea and was therefore chosen for combination treatment with immunoglobulins. The combination treatment reduced the diarrhea outcome measures significantly, prevented histopathological changes and reduced the virus load in the intestines. Conclusion The advantages associated with immunoglobulins and probiotics based therapy is that the treatment provides a rapid therapeutic effect and is cost efficient. These components do not require special storage conditions and could potentially complement the rehydration therapy that is currently used.

  1. The effect of prophylactic antipyretic administration on post-vaccination adverse reactions and antibody response in children: a systematic review.

    Directory of Open Access Journals (Sweden)

    Rashmi Ranjan Das

    Full Text Available Prophylactic antipyretic administration decreases the post-vaccination adverse reactions. Recent study finds that they may also decrease the antibody responses to several vaccine antigens. This systematic review aimed to assess the evidence for a relationship between prophylactic antipyretic administration, post-vaccination adverse events, and antibody response in children.A systematic search of major databases including MEDLINE and EMBASE was carried out till March 2014. Randomized controlled trials (RCTs comparing prophylactic antipyretic treatment versus placebo post-vaccination in children ≤ 6 years of age were included. Two reviewers independently applied eligibility criteria, assessed the studies for methodological quality, and extracted data [PROSPERO registration: CRD42014009717].Of 2579 citations retrieved, a total of 13 RCTs including 5077 children were included in the review. Prophylactic antipyretic administration significantly reduced the febrile reactions (≥ 38.0 °C after primary and booster vaccinations. Though there were statistically significant differences in the antibody responses between the two groups, the prophylactic PCM group had what would be considered protective levels of antibodies to all of the antigens given after the primary and booster vaccinations. No significant difference in the nasopharyngeal carriage rates (short-term and long-term of H. influenzae or S. pneumoniae serotypes was found between the prophylactic and no prophylactic PCM group. There was a significant reduction in the local and systemic symptoms after primary, but not booster vaccinations.Though prophylactic antipyretic administration leads to relief of the local and systemic symptoms after primary vaccinations, there is a reduction in antibody responses to some vaccine antigens without any effect on the nasopharyngeal carriage rates of S. pneumoniae & H. influenza serotypes. Future trials and surveillance programs should also aim at

  2. Effect of haemolysis and repeated freeze-thawing cycles on wild boar serum antibody testing by ELISA

    Directory of Open Access Journals (Sweden)

    Boadella Mariana

    2011-11-01

    Full Text Available Abstract Background Monitoring wildlife diseases is needed to identify changes in disease occurrence. Wildlife blood samples are valuable for this purpose but are often gathered haemolysed. To maximise information, sera often go through repeated analysis and freeze-thaw cycles. Herein, we used samples of clean and haemolysed Eurasian wild boar (Sus scrofa serum stored at -20°C and thawed up to five times to study the effects of both treatments on the outcome of a commercial ELISA test for the detection of antibodies against Suid Herpesvirus 1 (ADV. Results The estimated prevalence of antibodies against ADV was 50-53% for clean and haemolysed sera. Hence, haemolysis did not reduce the mean observed serum antibody prevalence. However, 10 samples changed their classification after repeated freeze-thawing. This included 3 (15% of the clean sera and 7 (41% of the haemolysed sera. Conclusions We recommend (1 establishing more restrictive cut-off values when testing wildlife sera, (2 recording serum quality prior to sample banking, (3 recording the number of freezing-thawing cycles and (4 store sera in various aliquots to reduce repeated usage. For instance, sera with more than 3 freeze-thaw cycles and a haemolysis of over 3 on a scale of 4 should better be discarded for serum antibody monitoring. Even clean (almost not haemolysed sera should not go through more than 5 freeze-thaw cycles.

  3. Differential effects of immunosuppressants and antibiotics on human monoclonal antibody production in SCID mouse ascites by five heterohybridomas.

    Science.gov (United States)

    Yoshinari, K; Arai, K

    1998-02-01

    SCID mice were inoculated with five human-mouse heterohybridomas derived by fusion of human lymph node lymphocytes from lung cancer patients with murine myeloma cells or human-mouse heteromyeloma cells, and the production of their human monoclonal antibodies (MAb) in the mouse ascites was investigated. In a comparison of the effects of pretreatment by i.p. (intraperitoneal) injection of pristane and anti-asialo GM1 serum on the antibody production of three of the hybridomas, pristane pretreatment resulted in substantial antibody production by all three, and pretreatment with anti-asialo GM1 serum resulted in similar or slightly lower levels of antibody production by two of the hybridomas but none by the third. In a second series of experiments using four of the hybridomas with pristane pretreatment, the co-injection of either penicillin G and streptomycin or kanamycin together with the hybridoma at the time of i.p. inoculation resulted in enhanced MAb production by the two heterohybridomas that had been propagated in medium containing hypoxanthine-aminopterin-thymidine (HAT) but not by the two that had been propagated in HAT-free medium. PMID:9523236

  4. The effect of treatment on the age-antibody relationship in children infected with Schistosoma mansoni and Schistosoma haematobium

    Directory of Open Access Journals (Sweden)

    Mutapi Francisca

    2002-01-01

    Full Text Available The effect of praziquantel treatment on the age-antibody relationship was studied in 174 children aged between 6 and 17 years from a schistosome endemic area in Zimbabwe. The children were co-infected with Schistosoma mansoni and S. haematobium with infection prevalences of 74% and 53% respectively. Antibody levels for the isotypes IgA, IgE, IgM, IgG1, IgG2, IgG3 and IgG4, directed against soluble egg antigen were measured using an indirect ELISA assay. Treatment resulted in a significant increase in levels of IgG2 and IgG3 while levels of IgA decreased significantly. In untreated children there were significant decreases in levels of IgG4. Treatment also resulted in significant alteration in the age-antibody profiles for the isotypes IgE, IgM, IgG1 and IgG2 in treated children but not in untreated children. The results are discussed in the context of factors believed to give rise to the age-antibody relationship; i.e. age-related exposure patterns, age-related development of acquired immunity, age-related hormonal changes and age-related changes in innate susceptibility to infection.

  5. Effects of Darwinian Selection and Mutability on Rate of Broadly Neutralizing Antibody Evolution during HIV-1 Infection.

    Science.gov (United States)

    Sheng, Zizhang; Schramm, Chaim A; Connors, Mark; Morris, Lynn; Mascola, John R; Kwong, Peter D; Shapiro, Lawrence

    2016-05-01

    Accumulation of somatic mutations in antibody variable regions is critical for antibody affinity maturation, with HIV-1 broadly neutralizing antibodies (bnAbs) generally requiring years to develop. We recently found that the rate at which mutations accumulate decreases over time, but the mechanism governing this slowing is unclear. In this study, we investigated whether natural selection and/or mutability of the antibody variable region contributed significantly to observed decrease in rate. We used longitudinally sampled sequences of immunoglobulin transcripts of single lineages from each of 3 donors, as determined by next generation sequencing. We estimated the evolutionary rates of the complementarity determining regions (CDRs), which are most significant for functional selection, and found they evolved about 1.5- to 2- fold faster than the framework regions. We also analyzed the presence of AID hotspots and coldspots at different points in lineage development and observed an average decrease in mutability of less than 10 percent over time. Altogether, the correlation between Darwinian selection strength and evolutionary rate trended toward significance, especially for CDRs, but cannot fully explain the observed changes in evolutionary rate. The mutability modulated by AID hotspots and coldspots changes correlated only weakly with evolutionary rates. The combined effects of Darwinian selection and mutability contribute substantially to, but do not fully explain, evolutionary rate change for HIV-1-targeting bnAb lineages. PMID:27191167

  6. Effect of concurrent intratracheal lipopolysaccharide and human serum albumin challenge on primary and secondary antibody responses in poultry.

    Science.gov (United States)

    Parmentier, H K; Klompen, A L; De Vries Reilingh, G; Lammers, A

    2008-10-01

    Activation of the innate immune system by pathogen-associated molecular patterns (PAMPs) may direct specific immune responses and as a consequence probably significantly affect vaccination. Previously, we described modulation of specific antibody responses to systemically administered model antigens by intravenously (i.v.) as well as intratracheally (i.t.) administered PAMP such as the endotoxin lipopolysaccharide (LPS). In this study effects of various doses of i.t.-administered LPS on primary and secondary specific total and individual isotype (IgM, IgG and IgA)-specific antibody responses of chickens simultaneously i.t. challenged with various doses of human serum albumin (HuSA) were determined. i.t.-administered LPS enhanced primary and secondary HuSA-specific total and isotype-specific antibody titers depending on the dose of LPS and the dose of simultaneously administered HuSA. i.t.-administered HuSA enhanced primary and secondary total antibody responses to 'environmental' LPS as shown in birds receiving the zero i.t. LPS treatment, which also depended on dose of HuSA. HuSA administration decreased antibody responses to high doses of LPS. Body weight gain as a measurement of an acute phase cachectin response to LPS was affected by a HuSA by LPS interaction, indicating that simultaneously administered higher doses of HuSA decreased LPS-induced cachectin responses of the birds. Our results suggest a complex interaction of innate and specific immune system activating airborne antigens, which may have significant consequences for vaccination and husbandry management procedures. PMID:18694797

  7. Effect of Eliminated the Breeding Pigs with Unqualified CSFV Antibody on Sows' Reproductive Performance and Pigs' Growth Performance

    Institute of Scientific and Technical Information of China (English)

    XIU Jin-sheng; WU Shun-yi; ZHOU Lun-jiang; YE Yao-hui; YU Dao-jin; CHEN Ru-jing; WANG Long-bai; ZHANG Xin-liang

    2011-01-01

    [Objective] The aim was to explore the effect of eliminated the breeding pigs with unqualified CSFV antibody on sow's reproductive performance and pig's growth performance so as to provide a scientific basis for the eliminating of the breeding pigs with unqualified CSFV antibody in large-scale pig farms. [Method] Serum samples from three scale pig farms were collected and tested with HerdChek CSFV-ELISA kit,then provided a certain scientific basis for scale pig farm to eliminate the unqualified( antibody blocking rate <50% ) breeders after booster immunization. [Result] After eliminating the breeding pigs with unqualified CSFV antibody, the average litter number of piglet in three pig farms ( A, B,C) were increased by 0.29 ( P<0.05), 0.40 ( P<0.01 ), 0.39 ( P<0.01 ) respectively; the average number of survival piglets were increased by 0.54 ( P < 0.01 ), 0.35 ( P < 0.01 ), 0.62 ( P < 0.01 ) respectively; the average litter number of weaned piglets were increased by 0.65 ( P <0.01 ), 0.71 ( P <0.01 ), 0.81 ( P < 0.01 ) respectively. The difference in weight gain of piglet at 30 - 60 d of age was extremely significant ( P <0.01 ), but inconspicuousness for the swine pregnancy rate, the survival rate of weaned piglet and piglet at 30 -60 d of age. [Conclusion] The eliminating the breeding pigs with unqualified CSFV antibody can significantly improve the performance of breeder and piglets.

  8. Effects of probiotic bacteria at different concentrations on production of immunomodulatory antibodies against rabies virus in vaccinated cattle

    Directory of Open Access Journals (Sweden)

    Renata Maria Bottino Vizzotto-Martino

    2016-02-01

    Full Text Available This study evaluated the effects of supplementation with a combination of probiotic microorganisms, added at different concentrations to the mineral mixture, on the production of serum antibodies against rabies virus in cattle vaccinated with a single dose of rabies vaccine. Forty-two male Nellore cattle, aged 12 months, were randomly divided into three groups (n = 14: the control group (CG received 70 grams of mineral mixture/animal/day; and the 2 gram probiotic group (G2P and 8 gram probiotic group (G8P received 70 grams of mineral mix/animal/day with 2 and 8 grams added, respectively, of a combination of probiotic microorganisms (Lactobacillus acidophilus, Streptococcus faecium, Bifidobacterium thermophilum and Bifidobacterium longum. Individual antibody titers were determined using a neutralization in cell-based rapid fluorescent focus inhibition test (RFFIT technique. One-way analysis of variance (one-way ANOVA was used with contrasts using the Tukey method to determine whether the experimental groups differed within each time point, and the paired t-test was used to determine whether differences occurred between time points within each group. The level of significance was set at 5%. There were statistically significant differences between the mean serum concentrations of the CG and G8P groups at 30 and 60 days after the first vaccination, and at 60 days, 100% of the animals maintained minimum titers of protective antibodies only in the G8P group. There was also improvement in the production of antibodies in the G2P group compared with the CG after 30 and 60 days, but this difference was not statistically significant. In conclusion, increasing doses of probiotic added to the mineral mix beneficially affected the rabies humoral immune response, as determined by serum antibodies, and enabled the maintenance of minimum protective titers for a longer period in previously vaccinated cattle.

  9. Effects of probiotic bacteria at different concentrations on production of immunomodulatory antibodies against rabies virus in vaccinated cattle

    OpenAIRE

    Renata Maria Bottino Vizzotto-Martino; Cristina Cecilia Augusto Vella Bonancéa; Thaís Cristina de Souza Geroti; Neuza Maria Frazati-Gallina; Paulo Eduardo Pardo; Hermann Bremer-Neto

    2016-01-01

    This study evaluated the effects of supplementation with a combination of probiotic microorganisms, added at different concentrations to the mineral mixture, on the production of serum antibodies against rabies virus in cattle vaccinated with a single dose of rabies vaccine. Forty-two male Nellore cattle, aged 12 months, were randomly divided into three groups (n = 14): the control group (CG) received 70 grams of mineral mixture/animal/day; and the 2 gram probiotic group (G2P) and 8 gram prob...

  10. Effect of previous vaccination with pneumococcal conjugate vaccine on pneumococcal polysaccharide vaccine antibody responses.

    Science.gov (United States)

    Schaballie, H; Wuyts, G; Dillaerts, D; Frans, G; Moens, L; Proesmans, M; Vermeulen, F; De Boeck, K; Meyts, I; Bossuyt, X

    2016-08-01

    During the past 10 years, pneumococcal conjugate vaccine (PCV) has become part of the standard childhood vaccination programme. This may impact upon the diagnosis of polysaccharide antibody deficiency by measurement of anti-polysaccharide immunoglobulin (Ig)G after immunization with unconjugated pneumococcal polysaccharide vaccine (PPV). Indeed, contrary to PPV, PCV induces a T-dependent, more pronounced memory response. The antibody response to PPV was studied retrospectively in patients referred for suspected humoral immunodeficiency. The study population was divided into four subgroups based on age (2-5 years versus ≥ 10 years) and time tested (1998-2005 versus 2010-12). Only 2-5-year-old children tested in 2010-12 had been vaccinated with PCV prior to PPV. The PCV primed group showed higher antibody responses for PCV-PPV shared serotypes 4 and 18C than the unprimed groups. To a lesser extent, this was also found for non-PCV serotype 9N, but not for non-PCV serotypes 19A and 8. Furthermore, PCV-priming elicited a higher IgG2 response. In conclusion, previous PCV vaccination affects antibody response to PPV for shared serotypes, but can also influence antibody response to some non-PCV serotypes (9N). With increasing number of serotypes included in PCV, the diagnostic assessment for polysaccharide antibody deficiency requires careful selection of serotypes that are not influenced by prior PCV (e.g. serotype 8). Further research is needed to identify more serotypes that are not influenced. PMID:26939935

  11. Measurement of salivary cortisol--effects of replacing polyester with cotton and switching antibody

    DEFF Research Database (Denmark)

    Hansen, Ase Marie; Garde, Anne Helene; Persson, Roger;

    2008-01-01

    measurements in our laboratory were affected by: 1) changes in the tampon material and 2) changes in the antibody of the analytical kit. In study 1, saliva from healthy subjects (n = 19) was split and spiked to Salivette polyester and cotton tampons, respectively, and treated as ordinary samples before being...... analysed for cortisol using a Spectria RIA kit for cortisol. In study 2, 68 anonymous saliva samples were analysed with the Spectria Cortisol RIA kit both before and after the manufacturer changed the antibody. The change from polyester to cotton tampons reduced the measured concentration of salivary...

  12. Effect of Levothyroxine Treatment on Clinical Symptoms in Hypothyroid Patients with Chronic Urticaria and Thyroid Autoimmunity

    Science.gov (United States)

    Kim, Do Hun; Sung, Nam Hee

    2016-01-01

    Background Thyroid autoimmunity has been increasingly reported to be associated with chronic urticaria (CU), and the possible clinical benefit of thyroid hormone or anti-thyroid drugs in some CU patients with autoimmune thyroid disease has been studied. However, the effect of thyroid hormone or anti-thyroid drugs on clinical symptoms of CU remains unclear. Objective We investigated the clinical response of urticaria to the treatment of thyroid dysfunction. Methods Medical records of patients with CU evaluated for thyroid autoimmunity and thyroid function were collected and reviewed. Results Of 184 patients with CU, 43 patients (23.4%) had thyroid autoantibodies and 26 patients (14.1%) had thyroid dysfunction. While none of the five patients with Graves' disease showed any improvement of urticaria after treatment with anti-thyroid drugs, two of the 10 patients with Hashimoto's thyroiditis showed improved urticaria after being treated with levothyroxine. Conclusion Although levothyroxine treatment was effective in a minority of patients with CU, there may be a causal relationship between CU and thyroid autoimmunity. PMID:27081267

  13. Effect of nerve activity on transport of nerve growth factor and dopamine β-hydroxylase antibodies in sympathetic neurones

    International Nuclear Information System (INIS)

    The effect of nerve activity on the uptake and retrograde transport of nerve growth factor (NGF) and dopamine β-hydroxylase (DBH) antibodies was studied by injecting 125I-labelled NGF and anti-DBH into the anterior eye chamber of guinea-pigs. Decentralization of the ipsilateral superior cervical ganglion (SCG) had no significant effect on the retrograde transport of either NGF or anti-DBH. Phenoxybenzamine produced a 50% increase in anti-DBH but not NGF accumulation and this effect was prevented by prior decentralization. This demonstrates that NGF is taken up independently of the retrieval of synaptic vesicle components. (Auth.)

  14. Pathogenic effects of maternal antinuclear antibodies during pregnancy in women with lupus

    Directory of Open Access Journals (Sweden)

    Rafael Herrera-Esparza

    2014-11-01

    Full Text Available Lupus is an autoimmune disease that primarily affects young women of childbearing age. Fertility rates in lupus patients depend on various factors, including disease activity, nephritis, and the presence of antiphospholipid antibodies; however, after lupus patients become pregnant, different factors may affect the course of pregnancy, such as the production of autoantibodies, pre-existing renal disease, and eclampsia, among others. The placenta is a temporary hemochorial organ that prevents immunological conflict due to exposure to alloantigens at the maternal-fetal interface; placental regulatory T cells play a major role in maternal-fetal tolerance. Typically, significant amounts of maternal IgG class antibodies cross the placenta and enter the fetal circulation. This transition depends on the distribution of Fc receptors along the syncytiotrophoblast. The production of antinuclear antibodies (ANA is a hallmark of lupus, and these autoantibodies can form immune complexes that are typically trapped in the placenta during gestation. However, the entry of ANA into the fetal circulation depends on the IgG-ANA concentration and the FcR placental density. Maternal antinuclear antibodies with anti-Ro or anti-La specificity might be pathogenic to the fetus if transfused by the placental pathway and could induce neonatal pathologies, such as neonatal lupus and congenital heart block. Here, we review the experimental and clinical data supporting a pathogenic role for maternal autoantibodies transmitted to the fetus

  15. Milk matrix effects on antibody binding analyzed by elisa and biolayer interferometry

    Science.gov (United States)

    Biolayer interferometry (BLI) was employed to study the impact of the milk matrix on the binding of ricin to asialofetuin (ASF) and to antibodies. This optical sensing platform utilized ligands immobilized covalently or via biotin-streptavidin linkage, and the results were compared to those obtained...

  16. Effect of thyroid auto-antibodies on hypothyroidism of adolescents with graves disease after 131I treatment

    International Nuclear Information System (INIS)

    To investigate the effect of TSH receptor antibody (TRAb) and thyroid peroxidase antibody (TPOAb) levels in adolescents with Graves disease (GD) before 131I treatment on the incidence of hypothyroidism after 131I therapy. The total 264 adolescent with GD were treated with 131I. All patients before the treatment were divided into A, B, C, D, E and F groups in accordance with the levels of TRAb and TPOAb in various combinations. The serum TSH, FT3, FT4, TRAb and TPOAb levels in all patients were measured after 131I treatment. The incidence of hypothyroidism within three years were observed in each group. The results showed that the incidence of hypothyroidism in TRAb negative group was higher than that of positive group (χ2=4.67, P2=4.10, 4.34, 5.66, P131I therapy. It could be cautious in treatment of GD adolescents of TRAb negative and TPOAb positive with 131I. (authors)

  17. The Effect of Antibody-Dependent Enhancement on the Transmission Dynamics and Persistence of Multiple-Strain Pathogens

    Science.gov (United States)

    Ferguson, Neil; Anderson, Roy; Gupta, Sunetra

    1999-01-01

    Cross-reactive antibodies produced by a mammalian host during infection by a particular microparasitic strain usually have the effect of reducing the probability of the host being infected by a different, but closely related, pathogen strain. Such cross-reactive immunological responses thereby induce between-strain competition within the pathogen population. However, in some cases such as dengue virus, evidence suggests that cross-reactive antibodies act to enhance rather than restrict the severity of a subsequent infection by another strain. This cooperative mechanism is thought to explain why pre-existing immunity to dengue virus is an important risk factor for the development of severe disease (i.e., dengue shock syndrome and dengue hemorrhagic fever). In this paper, we explore the effect of antibody-dependent enhancement on the transmission dynamics of multistrain pathogen populations. We show that enhancement frequently may generate complex and persistent cyclical or chaotic epidemic behavior. Furthermore, enhancement acts to permit the coexistence of all strains where in its absence only one or a subset would persist.

  18. Overexpression of CHOP alone and in combination with chaperones is effective in improving antibody production in mammalian cells.

    Science.gov (United States)

    Nishimiya, Daisuke; Mano, Takashi; Miyadai, Kenji; Yoshida, Hiroko; Takahashi, Tohru

    2013-03-01

    Secretory capacities including folding and assembly are believed to be limiting factors in the establishment of mammalian cell lines producing high levels of recombinant therapeutic proteins. To achieve industrial success, it is also important to improve protein folding, assembly, and secretory processes in combination with increasing transcription and translation. Here, we identified the expression of CHOP/Gadd153 and GRP78, which are unfolded protein response (UPR)-related genes, correlated with recombinant antibody production in stable CHO cells. Subsequently, CHOP overexpression resulted in increasing recombinant antibody production in some mammalian cell lines, and in addition a threefold further enhancement was obtained by combining expression with UPR-related genes or ER chaperones in transient assays. Overexpression of CHOP had no effect on the biochemical characteristics of the product. These results suggest overexpression of CHOP and its combinations may be an effective method to efficiently select a single cell line with a high level of antibody production in the development of cell lines for manufacturing. PMID:22926643

  19. Effects of anti-vascular endothelial growth factor monoclonal antibody (bevacizumab on lens epithelial cells

    Directory of Open Access Journals (Sweden)

    Jun JH

    2016-06-01

    Full Text Available Jong Hwa Jun,1 Wern-Joo Sohn,2 Youngkyun Lee,2 Jae-Young Kim21Department of Ophthalmology, School of Medicine, Dongsan Medical Center, Keimyung University, 2Department of Oral Biochemistry, School of Dentistry, IHBR, Kyungpook National University, Daegu, South KoreaAbstract: The molecular and cellular effects of anti-vascular endothelial growth factor monoclonal antibody (bevacizumab on lens epithelial cells (LECs were examined using both an immortalized human lens epithelial cell line and a porcine capsular bag model. After treatment with various concentrations of bevacizumab, cell viability and proliferation patterns were evaluated using the water-soluble tetrazolium salt assay and 5-bromo-2'-deoxyuridine enzyme-linked immunosorbent assay, respectively. The scratch assay and Western blot analysis were employed to validate the cell migration pattern and altered expression levels of signaling molecules related to the epithelial–mesenchymal transition (EMT. Application of bevacizumab induced a range of altered cellular events in a concentration-dependent manner. A 0.1–2 mg/mL concentration demonstrated dose-dependent increase in proliferation and viability of LECs. However, 4 mg/mL decreased cell proliferation and viability. Cell migrations displayed dose-dependent retardation from 0.1 mg/mL bevacizumab treatment. Transforming growth factor-β2 expression was markedly increased in a dose-dependent manner, and α-smooth muscle actin, matrix metalloproteinase-9, and vimentin expression levels showed dose-dependent changes in a B3 cell line. Microscopic observation of porcine capsular bag revealed changes in cellular morphology and a decline in cell density compared to the control after 2 mg/mL treatment. The central aspect of posterior capsule showed delayed confluence, and the factors related to EMT revealed similar expression patterns to those identified in the cell line. Based on these results, bevacizumab modulates the proliferation

  20. Effects of Sclerostin Antibody on the Healing of Femoral Fractures in Ovariectomised Rats.

    Science.gov (United States)

    Liu, Yang; Rui, Yunfeng; Cheng, Tin Yan; Huang, Shuo; Xu, Liangliang; Meng, Fanbiao; Lee, Wayne Yuk Wai; Zhang, Ting; Li, Nan; Li, Chaoyang; Ke, Huazhu; Li, Gang

    2016-03-01

    The inhibition of sclerostin by the systemic administration of a monoclonal antibody (Scl-Ab) significantly increased bone mass and strength in fractured bones in animal models and non-fractured bones in ovariectomised (OVX) rats. In this study, the effects of Scl-Ab on healing were examined in a closed fracture model in OVX rats. Sixty Sprague-Dawley rats underwent an ovariectomy or a sham operation at 4 months of age, and a closed fracture of the right femur was performed 3 months later. Subcutaneous injections with Scl-Ab (25 mg/kg) or saline were then administered on day 1 after the fracture and twice a week for 8 weeks (n = 20 per group), at which time the fractured femurs were harvested for micro-computed tomography analysis, four-point bending mechanical testing and histomorphometric analysis to examine bone mass, bone strength and dynamic bone formation at the fracture site. The angiogenesis at the fracture site was also examined. Bone marrow stem cells were also isolated from the fractured bone to perform a colony-forming unit (CFU) assay and an alkaline phosphatase-positive (ALP(+)) CFU assay. OVX rats treated with Scl-Ab for 8 weeks had significantly increased bone mineral density and relative bone volume compared with OVX rats treated with saline. Similarly, maximum loading, energy to maximum load and stiffness in Scl-Ab-treated OVX rats were significantly higher than those in saline controls. The mineral apposition rate (MAR), mineralising surface (MS/BS) and bone formation rate (BFR/BS) were also significantly increased in Scl-Ab-treated group compared with the saline-treated group in OVX rats. Furthermore, the Scl-Ab-treated group had more CFUs and ALP(+) CFUs than the saline-treated group in OVX rats. No significant difference in angiogenesis at the fracture site was found between the groups. Our study demonstrated that Scl-Ab helped to increase bone mass, bone strength and bone formation at the fracture site in a closed femoral fracture

  1. Sheep Monoclonal Antibodies Prevent Systemic Effects of Botulinum Neurotoxin A1

    Directory of Open Access Journals (Sweden)

    Charles B. Shoemaker

    2012-12-01

    Full Text Available Botulinum neurotoxin (BoNT is responsible for causing botulism, a potentially fatal disease characterized by paralysis of skeletal muscle. Existing specific treatments include polyclonal antisera derived from immunized humans or horses. Both preparations have similar drawbacks, including limited supply, risk of adverse effects and batch to batch variation. Here, we describe a panel of six highly protective sheep monoclonal antibodies (SMAbs derived from sheep immunized with BoNT/A1 toxoid (SMAbs 2G11, 4F7 or BoNT/A1 heavy chain C-terminus (HcC (SMAbs 1G4, 5E2, 5F7, 16F9 with or without subsequent challenge immunization with BoNT/A1 toxin. Although each SMAb bound BoNT/A1 toxin, differences in specificity for native and recombinant constituents of BoNT/A1 were observed. Structural differences were suggested by pI (5E2 = 8.2; 2G11 = 7.1; 4F7 = 8.8; 1G4 = 7.4; 5F7 = 8.0; 16F9 = 5.1. SMAb protective efficacy vs. 10,000 LD50 BoNT/A1 was evaluated using the mouse lethality assay. Although not protective alone, divalent and trivalent combinations of SMabs, IG4, 5F7 and/or 16F9 were highly protective. Divalent combinations containing 0.5–4 μg/SMAb (1–8 μg total SMAb were 100% protective against death with only mild signs of botulism observed; relative efficacy of each combination was 1G4 + 5F7 > 1G4 + 16F9 >> 5F7 + 16F9. The trivalent combination of 1G4 + 5F7 + 16F9 at 0.25 μg/SMAb (0.75 μg total SMAb was 100% protective against clinical signs and death. These results reflect levels of protective potency not reported previously.

  2. Effect of leukocyte antibodies and HLA matching on the intravascular recovery, survival, and tissue localization of 111-indium granulocytes

    International Nuclear Information System (INIS)

    The effect of leukocyte antibodies detected under different conditions on the fate in vivo of granulocytes was studied using 111-indium-labeled granulocytes. Sera from patients were tested by granulocyte agglutination (GA), granulocytotoxicity (GC), granulocyte immunofluorescence (GIF), lymphocytotoxicity (LC), and antibody-dependent lymphocyte-mediated granulocytotoxicity. Granulocytes from donors to be studied were labeled with 111-indium and injected. Then the intravascular recovery and survival or tissue localization was determined in 93 studies. Antibodies detected by granulocyte agglutination were associated with a significant reduction in recovery (6.7% v 30.8% in controls; P less than .001) and t1/2 (0.3 hours v 5.6 hours in controls; P = .002). When all possible combinations of serum reactivity were considered, reactivity in the GA plus GIF assays had the best correlation with decreased recovery (R2 = .49; P less than .001) and t1/2 (R2 = .73; P less than .001). When the relationship between the strength of antibody reactivity and the recovery and t1/2 were analyzed, the best relationship was between the combination of LC and GIF with recovery (R2 = .62; P = .001). Because of the general availability of the HLA (LC) testing, the role of LC reactivity was investigated in other ways. There was a strong relationship between sera highly reactive by LC and those reactive by GIF. These highly reactive sera were also associated with reduced recovery and t1/2. The influence of specific HLA antigen mismatches was also studied

  3. [Antibody therapy for Alzheimer's disease].

    Science.gov (United States)

    Tabira, Takeshi; Matsumoto, Shin-Ei; Jin, Haifeng

    2011-11-01

    In order to avoid Abeta-induced autoimmune encephalitis, several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different. It is unknown which antibody is effective for Alzheimer disease, and we must wait for the result of clinical trials. Some patients who developed tissue amyloid plaque immuno-reactive (TAPIR) antibody showed slower decline after AN-1792 vaccination. We developed TAPIR-like monoclonal antibody, which was found to react with Abeta oligomers preferentially. PMID:22277519

  4. In vitro effect of anti-β2 glycoprotein I antibodies on P-selectin expression, a marker of platelet activation

    Directory of Open Access Journals (Sweden)

    A. Hoxha

    2012-03-01

    Full Text Available Antiphospholipid antibodies (aPL associated with thromboembolic events and/or pregnancy morbidity characterize the so-called antiphospholipid syndrome (APS. Beta2glycoprotein I (β2GPI is the main target antigen for aPL, but the pathogenic role of anti-β2GPI antibodies (aβ2GPI is still unclear. Some authors assume they play a role in activating platelets. We evaluated the effects of aβ2GPI antibodies on platelet P-selectin expression. Aβ2GPI antibodies in the plasma of a pregnant APS patient were isolated by affinity chromatography at two different stages (catastrophic and quiescent of the disease. Gel filtered platelets (100 x 109/L from healthy volunteers were incubated with β2-GPI (20 µg/mL and with different concentrations (5. 25 and 50 µg/mL of aβ2GPI antibodies. P-selectin surface expression on platelets was assessed by flow cytometry using a specific fluorescent antibody directed against P-selectin. Aβ2GPI antibodies induced platelet activation only in the presence of thrombin receptor activator for peptide 6 (TRAP-6, a platelet agonist, at a subthreshold concentration. Aβ2GPI antibody enhancement on platelet surface P-selectin expression was stronger in the catastrophic than in the quiescent phase of the disease (47 vs 15%. TRAP-6 dependent platelet activation by aβ2GPI antibodies is consistent with the “two hit” pathogenetic hypothesis for thrombosis. Aβ2GPI antibodies induce higher platelet P-selectin expression during the active rather than the acute phases.

  5. Effect of anti-pilus antibodies on survival of gonococci within guinea pig subcutaneous chambers.

    OpenAIRE

    Lambden, P R; Heckels, J E; Watt, P.J.

    1982-01-01

    Guinea pigs were immunized with either alpha or beta pili from Neisseria gonorrhoeae P9 before the inoculation of subcutaneous chambers with a mixture of variants having alpha, beta, gamma, or delta pili. Animals immunized with alpha pili showed significant protection, but those immunized with beta pili did not. The degree of protection could be correlated with the cross-reactivity of the antibodies produced to the heterologous pilus types.

  6. Pathogenic effects of maternal antinuclear antibodies during pregnancy in women with lupus

    OpenAIRE

    Rafael Herrera-Esparza; Juan José Bollain-y-Goytia; Esperanza Avalos-Díaz

    2014-01-01

    Lupus is an autoimmune disease that primarily affects young women of childbearing age. Fertility rates in lupus patients depend on various factors, including disease activity, nephritis, and the presence of antiphospholipid antibodies; however, after lupus patients become pregnant, different factors may affect the course of pregnancy, such as the production of autoantibodies, pre-existing renal disease, and eclampsia, among others. The placenta is a temporary hemochorial organ that prevents i...

  7. Dynamic effects of antibody-dependent enhancement on the fitness of viruses

    OpenAIRE

    Cummings, Derek A. T.; Schwartz, Ira B.; Billings, Lora; Shaw, Leah B.; Burke, Donald S

    2005-01-01

    Antibody-dependent enhancement (ADE), a phenomenon in which viral replication is increased rather than decreased by immune sera, has been observed in vitro for a large number of viruses of public health importance, including flaviviruses, coronaviruses, and retroviruses. The most striking in vivo example of ADE in humans is dengue hemorrhagic fever, a disease in which ADE is thought to increase the severity of clinical manifestations of dengue virus infection by increasing virus replication. ...

  8. Effects of spacer parameters, modified monolayers, and patterned substrate on the capture efficiency of Escherichia coli-antibody based biosensing matrix

    Science.gov (United States)

    Cao, Ting

    2007-12-01

    To overcome the problem of losing bioactivity in covalent coupling in chemical sensor, a potential approach is to employ a long chain spacer to immobilize the antibody indirectly while maintaining separation of the biomolecule from the substrate. In this study, Poly (ethylene glycol) (PEG) spacers were employed for tethering E.Coli K99 pilus antibody to silicon wafer surfaces for the purpose of increasing the flexibility of antibody as well as reducing the steric hindrance. To illustrate the effect of spacer length, a series of spacer lengths were used to covalently attach the antibodies to silicon surfaces. XPS and AFM were used to characterize the surface morphology and chemical composition at each reaction step. The effect of spacer length in improving the specificity of immobilized antibody and the recognition process for bacteria-antibody was investigated by attaching E.Coli on the end of an AFM tip. Distribution of unbinding force and rupture distance from the force-distance curved obtained by AFM showed that the introduction of PEG spacer facilitates bacterial recognition which can improve the detected specific interaction up to 90%. J600 exhibited better flexibility in overcoming the steric hindrance experienced with direct immobilization than other spacer lengths. Moreover, binding efficiency, rupture distance and force distribution of bacteria-antibody pairs can be elucidated with AFM for measurement.

  9. Effects of Anti-NMDA Antibodies on Functional Recovery and Synaptic Rearrangement Following Hemicerebellectomy.

    Science.gov (United States)

    Laricchiuta, Daniela; Cavallucci, Virve; Cutuli, Debora; De Bartolo, Paola; Caporali, Paola; Foti, Francesca; Finke, Carsten; D'Amelio, Marcello; Manto, Mario; Petrosini, Laura

    2016-06-01

    The compensation that follows cerebellar lesions is based on synaptic modifications in many cortical and subcortical regions, although its cellular mechanisms are still unclear. Changes in glutamatergic receptor expression may represent the synaptic basis of the compensated state. We analyzed in rats the involvement of glutamatergic system of the cerebello-frontal network in the compensation following a right hemicerebellectomy. We evaluated motor performances, spatial competencies and molecular correlates in compensated hemicerebellectomized rats which in the frontal cortex contralateral to the hemicerebellectomy side received injections of anti-NMDA antibodies from patients affected by anti-NMDA encephalitis. In the compensated hemicerebellectomized rats, the frontal injections of anti-NMDA antibodies elicited a marked decompensation state characterized by slight worsening of the motor symptoms as well as severe impairment of spatial mnesic and procedural performances. Conversely, in the sham-operated group the frontal injections of anti-NMDA antibodies elicited slight motor and spatial impairment. The molecular analyses indicated that cerebellar compensatory processes were related to a relevant rearrangement of glutamatergic synapses (NMDA and AMPA receptors and other glutamatergic components) along the entire cortico-cerebellar network. The long-term maintenance of the rearranged glutamatergic activity plays a crucial role in the maintenance of recovered function. PMID:27027521

  10. Effects of an amyloid-beta 1-42 oligomers antibody screened from a phage display library in APP/PS1 transgenic mice

    Science.gov (United States)

    Wang, Jianping; Li, Nan; Ma, Jun; Gu, Zhiqiang; Yu, Lie; Fu, Xiaojie; Liu, Xi; Wang, Jian

    2016-01-01

    We screened anti-Aβ1-42 antibodies from a human Alzheimer’s disease (AD) specific single chain variable fragment (scFv) phage display library and assessed their effects in APP/PS1 transgenic mice. Reverse transcription-PCR was used to construct the scFv phage display library, and screening identified 11A5 as an anti-Aβ1-42 antibody. We mixed 11A5 and the monoclonal antibody 6E10 with Aβ1-42 and administered the mixture to Sprague-Dawley rats via intracerebroventricular injection. After 30 days, rats injected with the antibody/ Aβ1-42 mixture and those injected with Aβ1-42 alone were tested on the Morris water maze. We also injected 11A5 and 6E10 into APP/PS1 transgenic mice and assessed the concentrations of Aβ in brain and peripheral blood by ELISA at 1-month intervals for 3 months. Finally we evaluated behavior changes in the Morris water maze. Rats injected with Aβ1-42 and mixed antibodies showed better performance in the Morris water maze than did rats injected with Aβ1-42 alone. In APP/PS1 transgenic mice, Aβ concentration was lower in the brains of the antibody-treated group than in the control group, but higher in the peripheral blood. The antibody-treated mice also exhibited improved behavioral performance in the Morris water maze. In conclusion, anti-Aβ1-42 antibodies (11A5) screened from the human scFv antibody phage display library promoted the efflux or clearance of Aβ1-42 and effectively decreased the cerebral Aβ burden in an AD mouse model. PMID:26820640

  11. Effects of passage number on growth and productivity of hybridoma secreting MRSA anti-PBP2a monoclonal antibodies.

    Science.gov (United States)

    Corrêa, Arthur Luiz; Senna, José Procópio Moreno; de Sousa, Álvaro Paiva Braga

    2016-05-01

    Monoclonal antibodies (mAb) are high added value glycoproteins recommended for immunotherapy, diagnosis, and also for the treatment of bacterial infections resistant to multiple drugs such as Methicillin Resistant Staphylococcus aureus (MRSA). In addition to environmental conditions related to cell cultures, the intrinsic characteristics of hybridoma cells, like the secretion stability of monoclonal antibodies by the cells through successive subcultures, are relevant for the characterization of cell lines related to the productivity of mAb. The rate of mAb production differs significantly between different cell lines and different passage numbers, and it is an important variable in characterization of cell lines. In order to find a more robust, faster-growing, and higher-productivity cell line of hybridoma, cultivations in 24-well plates were performed in different subculture periods, or cell passages (P), of hybridoma cells producing MRSA anti-PBP2a monoclonal antibodies [MRSA-antiPBP2a (mAb)]. The objective of this study was to study the effects of cell growth and production of MRSA-antiPBP2a mAb secreted by murine hybridoma cells grown in different passages as well as determine the which passages the hybridomas can be cultivated without harming their growth and productivity. So, cell growth profiles of hybridomas secreting MRSA-antiPBP2a (mAb) and the production of MRSA-antiPBP2a mAb in different subculture periods or cell passages (P) were studied. Cell growth tests, monoclonal antibody productivity, and metabolite characteristics revealed substantial differences in those cells kept between P10 and P50. Similarities in the secretion of monoclonal antibody, growth, and metabolic profiles, were noted in the MRSA-antiPBP2a mAb producing hybridoma cells kept between P10 and P20. Also, glucose consumption (g/L) and lactate production (g/L) in the latter cell cultures were monitored daily through biochemical analyzer. As of P30, it was observed a 4.4 times reduction

  12. Effects of experimental immunosuppression in cattle with persistently high antibody levels to Salmonella Dublin lipopolysaccharide O-antigens

    Directory of Open Access Journals (Sweden)

    Nielsen Liza R

    2007-08-01

    transportation stress or dexamethasone treatment did not lead to excretion of S. Dublin in milk or faeces from infected animals. The study questions the general conception that cattle with persistently high antibody levels against S. Dublin O-antigens in naturally infected herds should be considered high risk for transmission and therefore culled as part of effective intervention strategies. It is suggested that the location of S. Dublin infected foci in the animal plays a major role for the risk of excreting bacteria.

  13. Effect of iodination site on binding of radiolabeled ligand by insulin antibodies and insulin autoantibodies

    International Nuclear Information System (INIS)

    Four human insulins and four porcine insulins, each monoiodinated to the same specific activity at one of the four tyrosine residues (A14, A19, B16, B26) and purified by reversed-phase liquid chromatography, were tested in a radiobinding assay against a panel of insulin-antibody (IA)-positive sera from 10 insulin-treated diabetics and insulin-autoantibody-positive (IAA) sera from 10 nondiabetics. Of the 10 IAA-positive sera, five were fully cross reactive with both insulin species, and five were specific for human insulin. The rank order of binding of sera with the four ligands from each species was random for IA (mean rank values of 1.9 for A14, 2.0 for A19, 2.5 for B16, and 3.6 for B26 from a possible ranking range of 1 to 4), but more consistent for non-human-insulin-specific IAA (mean rank values 1.3 for A14, 3.8 for A19, 1.7 for B16, and 3.2 for B26 for labeled human insulins; 1.2 for A14, 4.0 for A19, 1.8 for B16, and 3.0 for B26 for labeled porcine insulins). The rank order of binding was virtually uniform for human-insulin-specific IAA (mean values 1.2 for A14, 3.0 for A19, 1.8 for B16, and 4.0 for B26). The influence of iodination site on the binding of labeled insulin appears to be dependent on the proximity of the labeled tyrosine to the antibody binding site and the clonal diversity, or restriction, of insulin-binding antibodies in the test serum. When IA and IAA are measured, the implications of this study regarding the choice of assay ligand may be important

  14. Effect of Bovine Papillomavirus E2 Protein-Specific Monoclonal Antibodies on Papillomavirus DNA Replication

    OpenAIRE

    Kurg, Reet; Parik, Jüri; Juronen, Erkki; Sedman, Tiina; Abroi, Aare; Liiv,Ingrid; Langel, Ülo; Ustav, Mart

    1999-01-01

    The bovine papillomavirus type 1 (BPV-1) E2 protein is the master regulator of papillomavirus replication and transcription. We have raised a panel of monoclonal antibodies (MAbs) against the BPV-1 E2 protein and used them to probe the structure and function of the protein. Five MAbs reacted with linear epitopes, and four MAbs recognized conformation-dependent epitopes which mapped within the C-terminal DNA-binding and dimerization domain. MAb 1E2 was able to recognize the replication- and tr...

  15. In vitro effect of the lethal antibody on schistosomula in sera of rhesus monkeys immunized with highly x-irradiated cercariae. [Schistosoma mansoni, S. japonicum

    Energy Technology Data Exchange (ETDEWEB)

    Li Hs' u, S.Y.; Hs' u, H.F.; Isacson, P.; Kremenak, B.W.; Cheng, H.F.

    1976-12-01

    The in vitro effect of the lethal antibody on schistosomula in sera of rhesus monkeys immunized with highly x-irradiated cercariae of Schistosoma mansoni or S. japonicum was studied. In all 6 experimental monkeys, 4 unchallenged and 2 challenged, the effects of lethal antibody on schistosomula were demonstrated. The sera of the challenged monkeys had no stronger lethal effect than those of the unchallenged monkeys. This shows that the lethal antibody can be produced by the antigenic stimulation of schistosomula alone. The mortality rates of schistosomula in immune sera were already high at day 1, increased to a certain extent from day 1 to day 4, but showed no significant further increase in days 5 and 6. Two kinds of immunological reactions were observed: perischistosomular precipitate (PSP) and perischistosomular envelope (PSE). Schistosomula surrounded with PSP were usually dying or dead and those enclosed in PSE were usually alive and motile. Thus PSP may be related with the lethal antibody and PSE with a kind of enhancing antibody. Schistosomula with PSP showed a positive fluorescent reaction when stained with fluorescein-labeled rabbit anti-rhesus IgG. Scanning electron micrographs of schistosomula with PSP showed a highly degenerated tegument. These facts indicate that the antibody in PSP contains a fraction of IgG which acts on the tegument of schistosomula.

  16. Studies on pharmacological effects of Russell's viper and Saw-scaled viper venom and its neutralization by chicken egg yolk antibodies.

    Science.gov (United States)

    Meenatchisundaram, S; Parameswari, G; Michael, A; Ramalingam, S

    2008-08-01

    Antivenom antibodies were raised in 24-week-old white leghorn chickens against hemotoxic venoms of Russell's viper and Saw-scaled viper snakes. Booster injections of increasing concentrations of venom were given at 14days of time interval to raise the antivenom level in egg yolk. Antibodies were extracted from immunized chicken egg yolk by Polson et al. (Polson A., Von Wechmar M.B., Van Regenmortel M.H.V. Isolation of viral IgY antibodies from yolks of immunized hens. Immunological Communications 1980; 9:475-493.) and further purified by DEAE cellulose ion exchange column chromatography, which gave pure (180-200kDa) specific antibodies against venom. High titre of more than 1:10,000 antibodies were detected by ELISA at the 135th day of observation. The lethal toxicity and various pharmacological activities like hemorrhagic activity, phospholipase activity, edema and procoagulant activities of venom were carried out by both in vivo and in vitro methods. The effectiveness of antivenom in neutralizing these effects was carried out involving pre-incubation type experiments. The median effective dose (ED50) for Russell's viper venom was 0.96mg/2LD50/18g mice and for Saw-scaled viper venom it was 1.28mg/2LD50/18g mice. One millilitre of specific antivenom was effective in neutralizing 0.110mg of Russell's viper and 0.137mg of Saw-scaled viper venoms respectively (PD50). Antivenom was effective in neutralization assays in a dose dependent manner. The results indicate that antibodies raised in chicken could effectively neutralize the pharmacological effects induced by venoms and chickens therefore present an alternative and cheaper source of specific antibody generation. PMID:18550009

  17. Acute sleep deprivation has no lasting effects on the human antibody titer response following a novel influenza A H1N1 virus vaccination

    Directory of Open Access Journals (Sweden)

    Benedict Christian

    2012-01-01

    Full Text Available Abstract Background Experimental studies in humans have yielded evidence that adaptive immune function, including the production of antigen-specific antibodies, is distinctly impaired when sleep is deprived at the time of first antigen exposure. Here we examined the effects of a regular 24- hour sleep-wake cycle (including 8 hours of nocturnal sleep and a 24-hour period of continuous wakefulness on the 7-week antibody production in 11 males and 13 females in response to the H1N1 (swine flu virus vaccination. The specific antibody titer in serum was assayed by the hemagglutination inhibition test on the days 5, 10, 17, and 52 following vaccination. Results In comparison to the sleep group, sleep-deprived males but not females had reduced serum concentration of H1N1-specific antibodies five days after vaccination, whereas antibody titers at later time points did not differ between the conditions. Conclusions These findings concur with the notion that sleep is a supportive influence in the very early stage of an adaptive immune response to a viral antigen. However, our results do not support the view that acute sleep deprivation has lasting effects on the human antibody titer response to influenza vaccination.

  18. Theoretical study of catalytic efficiency of a Diels-Alderase catalytic antibody: an indirect effect produced during the maturation process.

    Science.gov (United States)

    Martí, Sergio; Andrés, Juan; Moliner, Vicent; Silla, Estanislao; Tuñón, Iñaki; Bertrán, Juan

    2008-01-01

    The Diels-Alder reaction is one of the most important and versatile transformations available to organic chemists for the construction of complex natural products, therapeutics agents, and synthetic materials. Given the lack of efficient enzymes capable of catalyzing this kind of reaction, it is of interest to ask whether a biological catalyst could be designed from an antibody-combining site. In the present work, a theoretical study of the different behavior of a germline catalytic antibody (CA) and its matured form, 39 A-11, that catalyze a Diels-Alder reaction has been carried out. A free-energy perturbation technique based on a hybrid quantum-mechanics/molecular-mechanics scheme, together with internal energy minimizations, has allowed free-energy profiles to be obtained for both CAs. The profiles show a smaller barrier for the matured form, which is in agreement with the experimental observation. Free-energy profiles were obtained with this methodology, thereby avoiding the much more demanding two-dimensional calculations of the energy surfaces that are normally required to study this kind of reaction. Structural analysis and energy evaluations of substrate-protein interactions have been performed from averaged structures, which allows understanding of how the single mutations carried out during the maturation process can be responsible for the observed fourfold enhancement of the catalytic rate constant. The conclusion is that the mutation effect in this studied germline CA produces a complex indirect effect through coupled movements of the backbone of the protein and the substrate. PMID:17960540

  19. Bispecific antibodies.

    Science.gov (United States)

    Kontermann, Roland E; Brinkmann, Ulrich

    2015-07-01

    Bispecific antibodies (bsAbs) combine specificities of two antibodies and simultaneously address different antigens or epitopes. BsAbs with 'two-target' functionality can interfere with multiple surface receptors or ligands associated, for example with cancer, proliferation or inflammatory processes. BsAbs can also place targets into close proximity, either to support protein complex formation on one cell, or to trigger contacts between cells. Examples of 'forced-connection' functionalities are bsAbs that support protein complexation in the clotting cascade, or tumor-targeted immune cell recruiters and/or activators. Following years of research and development (R&D), the first bsAb was approved in 2009. Another bsAb entered the market in December 2014 and several more are in clinical trials. Here, we describe the potentials of bsAbs to become the next wave of antibody-based therapies, focusing on molecules in clinical development. PMID:25728220

  20. The effects of variations in the specificities of the antibody components on a two-site immunoradiometric assay for ferritin

    International Nuclear Information System (INIS)

    Variations in the sub-unit antigenic structure of ferritins derived from various human tissues are reflected in the differing specificities of antisera raised against these ferritin preparations. In this study it was shown that antibody specificity played an important role in determining the sensitivity and overall binding of labelled antibody in a two-site immunoradiometric assay for ferritin. Homologous assay systems, in which solid phase and radiolabelled antibodies were of similar specificities, were generally less sensitive and showed lower binding than heterologous assay systems, in which solid phase and labelled antibodies were of different specificities. The source of the ferritin which was used as assay standard also played an important part in determining the sensitivity and overall binding in homologous antibody systems, spleen ferritin standards yielding assays superior to those obtained with placenta or liver ferritin standards. However, these differences between standards were not seen in a heterologous system employing solid phase antibodies directed against liver ferritin and labelled antibodies directed against placenta ferritin. The nature of the ferritin used to prepare immunoadsorbant for the purification of antibodies prior to radioiodination also affected the assay characteristics; antibodies prepared on spleen ferritin immunoadsorbant being more reactive than antibodies prepared on placenta ferritin immunoadsorbant, which in turn were more reactive then antibodies prepared on liver ferritin immunoadsorbant. (orig.)

  1. The effects of variations in the specificities of the antibody components on a two-site immunoradiometric assay for ferritin

    International Nuclear Information System (INIS)

    Variations in the sub-unit antigenic structure of ferritins derived from various human tissues are reflected in the differing specificities of antisera raised against these ferritin preparations. In this study it was shown that antibody specificity played an important role in determining the sensitivity and overall binding of labelled antibody in a two-site immunoradiometric assay for ferritin. Homologous assay systems, in which solid phase and radio-labelled antibodies were of similar specificities, were generally less sensitive and showed lower binding than heterologous assay systems, in which solid phase and labelled antibodies were of different specificities. The source of the ferritin which was used as assay standard also played an important part in determining the sensitivity and overall binding in homologous antibody systems, spleen ferritin standards yielding assays superior to those obtained with placenta or liver ferritin standards. However, these differences between standards were not seen in a heterologous system employing solid-phase antibodies directed against liver ferritin and labelled antibodies directed against placenta ferritin. The nature of the ferritin used to prepare immunoadsorbant for the purification of antibodies before radioiodination also affected the assay characteristics; antibodies prepared on spleen ferritin immunoadsorbant being more reactive than antibodies prepared on placenta ferritin immunoadsorbant, which in turn were more reactive than antibodies prepared on liver ferritin immunoadsorbant. (author)

  2. Novel human single chain antibody fragments that are rapidly interalizing effectively target epithelioid and sarcomatoid mesotheliomas

    Science.gov (United States)

    Iyer, Arun K.; Lan, Xiaoli; Zhu, Xiaodong; Su, Yang; Feng, Jinjin; Zhang, Xiaoju; Gao, Dongwei; Seo, Youngho; VanBrocklin, Henry F.; Broaddus, V. Courtney; Liu, Bin; He, Jiang

    2011-01-01

    Human antibodies targeting all subtypes of mesothelioma could be useful to image and treat this deadly disease. Here we report tumor targeting of a novel internalizing human single chain antibody fragment (scFv) labeled with 99mTc (99mTc-M40) in murine models of mesothelioma of both epithelioid (M28) and sarcomatoid (VAMT-1) origins. 99mTc-M40 was taken up rapidly and specifically by both subtype tumor cells in vitro, with 68–92% internalized within 1h. The specificity of binding was evidenced by blocking (up to 95%) with 10-fold excess of unlabeled M40. In animal studies, tumors of both subtypes were clearly visualized by SPECT/CT as early as 1h post-injection of 99mTc-M40. Tumor uptake measured as percent of injected dose per gram tissue (%ID/g) at 3h was 4.38 and 5.84 for M28 and VAMT-1 tumors respectively, significantly greater than all organs or tissues studied (liver, 2.62%ID/g; other organs or tissues <1.7%ID/g), except the kidneys (130.7%ID/g), giving tumor-to-blood ratios of 5:1 and 7:1 and tumor-to-muscle ratios of 45:1 and 60:1, for M28 and VAMT-1 respectively. The target-mediated uptake was confirmed by a nearly 70% reduction in tumor activity following administration of 10-fold excess of unlabeled scFv. Taken together, these results indicate that M40 can rapidly and specifically target epithelioid and sarcomatoid tumor cells, demonstrating the potential of this agent as a versatile targeting ligand for imaging and therapy of all subtypes of mesothelioma. PMID:21447742

  3. Effect of chloramine-T labeling conditions on the stability of monoclonal antibodies and their fragments

    International Nuclear Information System (INIS)

    Rapid in vivo degradation of radioiodinated monoclonal antibodies (MAb) has been reported. Conditions for radioiodination have varied. The purposes of this study were to compare the stability of MAb and their fragments when iodinated with chloramine-T (CT) under different conditions, and to compare methods for quality assessment of the radioiodinated molecules. A B-cell lymphoma MAb (Lym-1, IgG2a) and its FAb fragment, and a mammary cancer MAb(B6.01, IgG1) and its F(Ab')/sub 2/ fragment were iodinated with I-125 at CT:AB and I:Ab ratios of 1:1 and 1:10. Molecular sieving (TSK-3000) high performance liquid chromatography (HPLC), cellulose acetate electrophoresis (CAE) at 11 and 45 minutes and solid phase immunoreactivity (IRA) were used to observe stability of the molecules when stored at 40C. Radiochemical yield was greater than 95% in all instances. Iodination at CT:Ab and I:Ab ratios of 1:1 induced progressive degradation in all species which was most marked for the fragments. Iodination at CT:Ab and I:Ab ratios of 1:10 resulted in no observable degradation over 21 days. There was no significant difference in degradation between the IgG2a and IgG1 antibody when iodinated under identical circumstances. HPLC, CAE for 11 minutes and IRA, but not CAE for 45 minutes, revealed comparable changes. The authors conclude that lesser amounts of chloramine-T can be used to iodinate MAb and their fragments without loss of radiochemical efficiency and with improved stability of the species. MAb fragments are more vulnerable to chloramine-T. These observations may explain, at least in part, rapid in vivo degradation of radioiodinated MAb

  4. Decrease in binding ability of IgG antibodies by lymphocyte receptors as a result of low dose irradiation effect

    International Nuclear Information System (INIS)

    The effect of low dose irradiation on binding of IgG antibodies by B lymphocyte receptors in peripheral blood is studied for practically health people, living in the Minsk region, and for those people, who live on territories with a high radiation background. A method to determine BIgG+ lymphocytes, carrying the corresponding immunoglobulin determinants (IgA, IgM, IgG, IgD or IgE), in smears was developed and used. Irradiation doses were determined as a sum of contributions of external and internal irradiation. The data on the content of BIgG+ lymphocytes in peripheral blood of the patients depending on their age and irradiation dose are given. The conclusion is made that binding of IgG antibodies by lymphocyte receptors is sensitive to low irradiation doses. The account of BIgG+ lymphocytes in peripheral blood can be useful in formation of groups having increased risk of oncological disease accurrence. 4 refs.; 1 tab

  5. Effects of gamma radiation immunogenicity of ribonucleoprotein (RNPs) of rabies virus and purification of anti-RNPs antibodies for diagnosis

    International Nuclear Information System (INIS)

    The World Health Organization recommends the direct immunofluorescence test for laboratory diagnosis and serological evaluation of rabies. To achieve this test, fluorescent anti-ribo nucleoproteins (RNPs) conjugates, produced from purified IgGs of RNP-immunized animals are employed. The aims of the present study were: investigate the effects of gamma radiation on the immunogenicity of RNPs, as well as to compare two chromatographic methodologies for the purification of anti-RNPs immunoglobulins. Sera from animals immunized with either native or irradiated RNPs were compared by direct immunofluorescence and immuno enzymatic assays. Our results indicate that the animals immunized with irradiated antigen requested a lower number of doses to reach high antibody titers. The immunofluorescence assays indicated that the conjugates produced with the anti-irradiated RNPs IgGs showed similar specificity to its anti-native counterpart, but with a higher definition of the virus inclusions. The purification methods were compared by Bradford and electrophoresis assays. According to the results, we concluded that the affinity-based process resulted in higher yields, lower execution time, and higher purity of the antibodies. (author)

  6. Antibody Therapy Targeting CD47 and CD271 Effectively Suppresses Melanoma Metastasis in Patient-Derived Xenografts.

    Science.gov (United States)

    Ngo, Michael; Han, Arum; Lakatos, Anita; Sahoo, Debashis; Hachey, Stephanie J; Weiskopf, Kipp; Beck, Andrew H; Weissman, Irving L; Boiko, Alexander D

    2016-08-01

    The high rate of metastasis and recurrence among melanoma patients indicates the existence of cells within melanoma that have the ability to both initiate metastatic programs and bypass immune recognition. Here, we identify CD47 as a regulator of melanoma tumor metastasis and immune evasion. Protein and gene expression analysis of clinical melanoma samples reveals that CD47, an anti-phagocytic signal, correlates with melanoma metastasis. Antibody-mediated blockade of CD47 coupled with targeting of CD271(+) melanoma cells strongly inhibits tumor metastasis in patient-derived xenografts. This therapeutic effect is mediated by drastic changes in the tumor and metastatic site immune microenvironments, both of whichwhich exhibit greatly increased density of differentiated macrophages and significantly fewer inflammatory monocytes, pro-metastatic macrophages (CCR2(+)/VEGFR1(+)), and neutrophils, all of which are associated with disease progression. Thus, antibody therapy that activates the innate immune response in combination with selective targeting of CD271(+) melanoma cells represents a powerful therapeutic approach against metastatic melanoma. PMID:27477289

  7. Protective Effect of an Antibody against Specific Extracellular Domain of TLR2 on Agonists-Driven Inflammatory and Allergic Response

    Science.gov (United States)

    Guo, Tianwu; Cai, Jun; Peng, Yanxia; Zhang, Lifang; Lan, Qiaofen; Chen, Yanwen; Liao, Huanjin; Xie, Tong; Wu, Ping; Pan, Qingjun

    2016-01-01

    Specific blocking strategies of TLR2-mediated inflammatory signaling and hypersensitivity reactions may offer novel therapeutic strategies to prevent a variety of diseases. In this study, we investigated the blocking effects of a new anti-TLR2 antibody anti-T20 against a 20 mer peptide T20 located in the extracellular specific domain of mouse TLR2. In addition, the effects of the anti-T20 in vitro, measuring the inhibition of the IL-6 and TNF-α production in response to PGN, LTA, and Pam3CSK4-stimulated RAW264.7 cells, were determined. In vivo, the effects of anti-T20 on a lethal anaphylaxis model using PGN-challenged OVA allergic mice, including the rectal temperature and mortality, and serum levels of TNF-α, IL-6, and LTC4 were assayed. The results showed that anti-T20 specifically bound to TLR2 and significantly inhibited PGN, LTA, and Pam3CSK4-driven TNF-α and IL-6 production by RAW264.7 cells. Also, anti-T20 protected OVA allergic mice from PGN-induced lethal anaphylaxis, and the serum levels of TNF-α, IL-6, and LTC4 of anti-T20 treated PGN-challenged OVA allergic mice were decreased as compared to isotype control of anti-T20 treated mice. In summary, this study produced a new antibody against the specific extracellular domain of TLR2 which has protective effect on TLR2 agonists-driven inflammatory and allergic response.

  8. Effects of poly lactic-co-glycolic acid-Nogo A antibody delayed-release microspheres on regeneration of injured spinal cord in rats

    Institute of Scientific and Technical Information of China (English)

    Hai Lan; Yueming Song

    2009-01-01

    BACKGROUND: Nogo A antigen is the major inhibiting factor blocking regeneration of the injured spinal cord. Neutralizing Nogo A antigens using Nogo A antibodies may help promote neurite regeneration and nervous function recovery. For successful regeneration, sustained release of the antibody from a biodegradable material loaded with Nogo A antibodies to the injury site is required. OBJECTIVE: To compare the therapeutic effects of poly lactic-co-glycolic acid (PLGA)-Nogo A antibody delayed-release microspheres and Nogo A antibody alone on spinal regeneration in Sprague-Dawley rats with complete transverse injury to the spinal cord.DESIGN, TIME AND SETTING: A randomized, controlled animal trial was performed at the Pharmacological Laboratory of West China Center of Medical Sciences, Sichuan University, between October 2007 and January 2008.MATERIALS: Goat anti-rat Nogo A monoclonal antibody was purchased from Santa, American; goat anti-rat neurofilament 200 monoclonal antibody was from Zhongshan Goldenbridge, Beijing, China; PLGA-Nogo A antibody delayed-release microspheres were provided by the College of Pharmacy, Sichuan University.METHODS: A total of 36 adult female Sprague Dawley rats were used to establish models of completely transected spinal cord injury, at T10. Animals were randomly divided into three groups (n=12): model, Nogo A antibody alone, and Nogo A antibody delayed-release microsphere groups. After transverse injury of the spinal cord, 50 μL normal saline solution, 50 μL normal saline solution containing 50 μ g Nogo A antibody, and 50 μ L normal saline solution containing 50 μg Nogo A antibody microspheres were administered to the respective groups at the injury site. MAIN OUTCOME MEASURES: The expression of Nogo A and neurofilament 200 in injured spinal cord was tested immunohistochemically, and motor function of rats was assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale.RESULTS: Four weeks after injury, expression of Nogo A in

  9. Uses of monoclonal antibody 8H9

    Science.gov (United States)

    Cheung, Nai-Kong V.

    2013-04-09

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides different uses of the monoclonal antibody 8H9 or its derivative.

  10. Protective effects of anti-ricin A-chain antibodies delivered intracellularly against ricin-induced cytotoxicity

    Institute of Scientific and Technical Information of China (English)

    Frank; Martiniuk; Seth; Pincus; Sybille; Müller; Heinz; Kohler; Kam-Meng; Tchou-Wong

    2010-01-01

    AIM:To evaluate the ability of anti-ricin A-chain antibodies,delivered intracellularly,to protect against ricininduced cytotoxicity in RAW264.7 cells. METHODS:Anti-deglycosylated ricin A-chain antibody and RAC18 anti-ricin A-chain monoclonal antibody were delivered intracellularly by encapsulating in liposomes or via conjugation with the cell-penetrating MTS-transport peptide.RAW264.7 cells were incubatedwith these antibodies either before or after ricin exposure.The changes in cytotoxicity were estimated by MTT assay.Co-localization of internalized antibody and ricin was evaluated by fluorescence microscopy. RESULTS:Internalized antibodies significantly increased cell viability either before or after ricin exposure compared to the unconjugated antibodies.Fluorescence microscopy confirmed the co-localization of internalized antibodies and ricin inside the cells. CONCLUSION:Intracellular delivery of antibodies to neutralize the ricin toxin after cellular uptake supports the potential use of cell-permeable antibodies for postexposure treatment of ricin intoxication.

  11. Effects of antibodies induced by a conjugate vaccine on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone absorptive transport, metabolism, and proliferation of human lung cells.

    Science.gov (United States)

    De Buck, Stefan S; Schellenberger, Mario T; Ensch, Corinne; Muller, Claude P

    2010-08-01

    One of the most abundant and potent lung carcinogen is the nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The monoclonal antibody P9D5 induced with a NNK-conjugate vaccine was used to investigate the ability of NNK-specific antibodies to modulate NNK-induced adverse effects as well as its absorptive transport and metabolism in two lung cancer cell lines (Calu-3 and NCI-H82). Transport experiments in Calu-3 cells with a 50-fold molar excess of apical P9D5 increased the recovery of coadministered apical NNK, with a concomitant decrease in NNK transepithelial transport of more than 50% compared to controls. In contrast, basolateral P9D5 did neither influence transepithelial transport of NNK nor its disappearance from the apical compartment. Calu-3 cells were also found to reduce NNK to NNAL and a 65-fold molar excess of NNK-specific antibody inhibited this metabolic conversion by 46 and 54% compared to irrelevant control antibody after 48 and 72 hr, respectively. The biological relevance of NNK redistribution by antibody was demonstrated by reversion of NNK-induced cell proliferation in NCI-H82 cells. Repartitioning of tobacco carcinogens by antibody may reduce their early effective peak concentrations in susceptible target organs and thus relieve overloaded local DNA repair mechanisms and diminish carcinogen-induced cell proliferation. These in vitro data therefore suggest that a prophylactic antibody response may be associated with a reduced risk of cancer. PMID:19960439

  12. Harmful Effect of Anti-Class II Antibodies in Kidney Transplant Patients who Experienced an Acute Rejection Episode

    OpenAIRE

    Berthou, F.; Absi, L.; Mariat, C; Alamartine, E.; M. Phayphet

    2006-01-01

    The presence of anti-lymphocytes antibodies is associated with the occurrence of acute rejection after kidney transplantation but few is known on their role after the rejection episode. We conducted a retrospective study in kidney transplant recipients who experienced a biopsy proven acute rejection episode to analyse the influence of anti-lymphocytes antibodies on clinical outcome. Anti-lymphocytes antibodies were detected before and after transplantation and characterized for isotype, class...

  13. Radioiodinated antibody targeting of the HER-2/neu oncoprotein: effects of labeling method on cellular processing and tissue distribution

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, M.R. E-mail: zalut001@mc.duke.edu; Xu, F.J.; Yu, Y.; Foulon, C.F.; Zhao, X.-G.; Slade, S.K.; Affleck, D.J.; Bast, R.C

    1999-10-01

    Monoclonal antibody (MAb) internalization can have a major effect on tumor retention of radiolabel. Two anti-HER-2/neu MAbs (TA1 and 520C9) were radioiodinated using the iodogen, N-succinimidyl 5-iodo-3-pyridinecarboxylate (SIPC), and tyramine-cellobiose (TCB) methods. Paired-label studies compared internalization and cellular processing of the labeled MAbs by SKOv3 9002-18 ovarian cancer cells in vitro. Intracellular radioiodine activity for 520C9 was up to 2.6 and 3.0 times higher for SIPC and TCB labeling, respectively, compared with iodogen. Likewise, intracellular activity for TA1 was up to 2.3 and 2.9 times higher with the SIPC and TCB methods compared with iodogen labeling. Unfortunately, similar advantages in tumor accumulation were not achieved in athymic mice bearing SKOv3 9008-18 ovarian cancer xenografts.

  14. Radioiodinated antibody targeting of the HER-2/neu oncoprotein: effects of labeling method on cellular processing and tissue distribution

    International Nuclear Information System (INIS)

    Monoclonal antibody (MAb) internalization can have a major effect on tumor retention of radiolabel. Two anti-HER-2/neu MAbs (TA1 and 520C9) were radioiodinated using the iodogen, N-succinimidyl 5-iodo-3-pyridinecarboxylate (SIPC), and tyramine-cellobiose (TCB) methods. Paired-label studies compared internalization and cellular processing of the labeled MAbs by SKOv3 9002-18 ovarian cancer cells in vitro. Intracellular radioiodine activity for 520C9 was up to 2.6 and 3.0 times higher for SIPC and TCB labeling, respectively, compared with iodogen. Likewise, intracellular activity for TA1 was up to 2.3 and 2.9 times higher with the SIPC and TCB methods compared with iodogen labeling. Unfortunately, similar advantages in tumor accumulation were not achieved in athymic mice bearing SKOv3 9008-18 ovarian cancer xenografts

  15. Effects of Inula Britannica on the production of antibodies and cytokines and on T cell differentiation in C57BL/6 mice immunized by ovalbumin.

    Science.gov (United States)

    Song, Qing-Hua; Kobayashi, Takao; Hong, Tie; Cyong, Jong-Chol

    2002-01-01

    In this study, we investigated the effects of Inula Britannica on the production of antibodies against ovalbumin, and the differentiation of T cells, in C57BL/6 mice. The oral administration of Inula Britannica suppressed IL-4 and IL-6 production in lymphocytes collected from an inguinal lymph node in the immunized leg. On the other hand, the intraperitoneal administration of Inula Britannica suppressed IgG1 production, the ratio of IFN-gamma+IL-4-/IFN-gamma-IL-4+ cells and cytokine production of IL-6. It was presumed that the effects of Inula Britannica on the production of antibodies were induced by regulation of the balance of Th1 and Th2. Further, IL-4 and IL-6 production by lymphocytes collected from an inguinal lymph node in the immunized leg were suppressed, and therefore production of antibodies was suppressed. PMID:12230018

  16. Evaluation of the effects of dexamethasone-induced stress on levels of natural antibodies in immunized laying hens.

    Science.gov (United States)

    Cecchini, Stefano; Rossetti, Michele; Tomaso, Francesco Di; Caputo, Anna Rocchina

    2016-09-01

    Natural antibodies (NAb) are an important humoral component of innate immunity, playing a pivotal role as first line of defence against pathogens even without prior antigen-specific activation or antigen-driven selection. The levels of NAb in plasma of young laying hens were explored in more detail and identified 2,4,6-trinitrophenyl bovine serum albumin (TNP-BSA), as the non-self antigen showing the highest levels of IgΥ- and IgM-NAb. Subsequently, the relation between specific antibody (SpAb) levels and NAb levels, and the effect of dexamethasone (DEX)-induced stress on the acquired Ab response and on NAb levels were examined. According to obtained results, the affinity of NAb and SpAb, measured using the thiocyanate elution method, resulted higher in SpAb than in NAb. After stress induction, IgM-NAb and SpAb levels showed a transient decrease, whereas the levels of IgΥ-NAb were not changed. Moreover, statistical analysis showed positive correlations between IgΥ- and IgM-NAb levels and between IgM-NAb and SpAb levels that are lost as stress has been induced, whereas no correlation was observed between IgΥ-NAb and SpAb levels, neither before nor after the DEX-administration. This indicates that IgM-NAb assessment could be a valid tool to estimate the potential of the acquired Ab response and that the dexamethasone-induced stress condition causes depression of IgM-NAb levels and the acquired Ab response, but it has no evaluable effects on IgΥ-NAb levels. PMID:27436442

  17. Monoclonal antibodies in rheumatoid arthritis: comparative effectiveness of tocilizumab with tumor necrosis factor inhibitors

    Directory of Open Access Journals (Sweden)

    Tanaka T

    2014-04-01

    Full Text Available Toshio Tanaka,1,2 Yoshihiro Hishitani,3 Atsushi Ogata2,3 1Department of Clinical Application of Biologics, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan; 2Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan; 3Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan Abstract: Rheumatoid arthritis (RA is a chronic inflammatory disease characterized by persistent joint inflammation, systemic inflammation, and immunological abnormalities. Because cytokines such as tumor necrosis factor (TNF-α and interleukin (IL-6 play a major role in the development of RA, their targeting could constitute a reasonable novel therapeutic strategy for treating RA. Indeed, worldwide clinical trials of TNF inhibiting biologic disease modifying antirheumatic drugs (bDMARDs including infliximab, adalimumab, golimumab, certolizumab pegol, and etanercept as well as the humanized anti-human IL-6 receptor antibody, tocilizumab, have demonstrated outstanding clinical efficacy and tolerable safety profiles, resulting in worldwide approval for using these bDMARDs to treat moderate to severe active RA in patients with an inadequate response to synthetic disease modifying antirheumatic drugs (sDMARDs. Although bDMARDs have elicited to a paradigm shift in the treatment of RA due to the prominent efficacy that had not been previously achieved by sDMARDs, a substantial percentage of patients failed primary or secondary responses to bDMARD therapy. Because RA is a heterogeneous disease in which TNF-α and IL-6 play overlapping but distinct pathological roles, further studies are required to determine the best use of TNF inhibitors and tocilizumab in individual RA patients. Keywords: interleukin-6, rheumatoid arthritis, adalimumab, biologic

  18. Effects of the Monoclonal Antibody against Porcine 40 kDa Adipocyte-specific Plasma Membrane Protein on Adipocytes and Carcass Composition

    Institute of Scientific and Technical Information of China (English)

    Shizheng GAO; Changrong GE; Xi ZHANG; Yonggang LIU

    2007-01-01

    The effects of the mouse monoclonal antibody against 40 kDa adipocyte-specific plasma membrane protein on porcine adipocytes and carcass composition were investigated in vitro and in vivo.Results revealed that the in vitro complement-mediated cytotoxicity of this monoclonal antibody can lead to adipocyte lysis, remarkable reduction of adipocyte lipid accumulation (P<0.01), and significant decrease of well-differentiated fat cells (P<0.01). Treatment of adipocytes with this antibody alone in vitro did not induce cell lysis, but could lead to noticeable reduction of well-differentiated cells and lipid accumulation (P<0.05) at the pre-adipocyte stage. In vivo, pigs injected with 0.5 mg/kg or 1.0 mg/kg of antibody showed smaller adipocyte sizes (P<0.01) and reduced lipid accumulation of adipocytes (P<0.01). Our results also indicated that pigs intraperitoneally or subcutaneously immunized with 0.5 mg/kg of monoclonal antibody at 15 kg or 1.0 mg/kg antibody at 60 kg had a higher lean meat percentage (P<0.05), larger loin eye area (P<0.05), lower fat meat percentage (P<0.05), less backfat thickness (P<0.05) and smaller leaf fat weight (P<0.05) than the control pigs, but other carcass traits such as caul fat weight, heart weight, liver weight, spleen weight,kidney weight, lung weight, and dressing percentage were not significantly affected. These results suggested that this monoclonal antibody could be applied to restrain excessive fat deposition in porcine production.

  19. Measurement of anti-DFS70 antibodies in patients with ANA-associated autoimmune rheumatic diseases suspicion is cost-effective.

    Science.gov (United States)

    Gundín, Simón; Irure-Ventura, Juan; Asensio, Esther; Ramos, David; Mahler, Michael; Martínez-Taboada, Victor; López-Hoyos, Marcos

    2016-12-01

    The presence of antinuclear antibodies (ANA) is associated with a wide range of ANA-associated autoimmune rheumatic diseases (AARD). The most commonly method used for the detection of ANA is indirect immunofluorescence (IIF) on HEp-2 cells. This method is very sensitive but unspecific. As a consequence, ANA testing on HEp-2 substrates outside a proper clinical specialist framework may lead to inappropriate referrals to tertiary care specialists and, worst case inappropriate and potentially toxic therapy for the patient. Among ANA, isolated anti-DFS70 antibodies represent a potentially important biomarker that can be clinically used to discriminate AARD from non-AARD patients in ANA IIF positive individuals. Therefore, their presence may avoid unnecessary follow-up testing and referrals. In our study, we investigated if the implementation of a new ANA workup algorithm allowing for the identification of anti-DFS70 antibodies is cost-effective through the reduction of both unnecessary follow-up testing and outpatient clinic visits generated by the clinical suspicion of a potential AARD. None of the 181 patients included with a positive monospecific anti-DFS70 antibody result developed SARD during the follow-up period of 10 years. The reduction in number of tests after ANA and anti-DFS70 positive results was significant for anti-ENA (230 vs. 114 tests; p < 0.001) and anti-dsDNA antibodies (448 vs. 114 tests; p < 0.001). In addition, the outpatient clinic visits decreased by 70 % (p < 0.001). In total, the adoption of the new algorithm including anti-DFS70 antibody testing resulted in a cost saving of 60869.53 € for this pilot study. In conclusion, the use of anti-DFS70 antibodies was clearly cost-efficient in our setting. PMID:27473142

  20. Monoclonal antibodies to the insulin receptor mimic metabolic effects of insulin but do not stimulate receptor autophosphorylation in transfected NIH 3T3 fibroblasts

    International Nuclear Information System (INIS)

    The metabolic actions of insulin and anti-insulin receptor monoclonal antibodies were compared with their effects on insulin receptor phosphorylation in mouse NIH 3T3 fibroblasts transfected with human insulin receptor cDNA. In serum-starved NIH 3T3 HIR3.5 cells, uptake of 2-deoxy-[3H]glucose was stimulated up to 2-fold after 30 min with insulin, with a half-maximal effect at 0.1 nM insulin. Incorporation of [3H]thymidine was stimulated ∼ 12-fold after a 16-hr preincubation with insulin, with a half-maximal effect at 2 nM insulin. Phosphorylation of insulin receptor β-subunit in cells prelabeled with [32P]phosphate was increased 10- to 20-fold within 5 min of adding insulin. Monoclonal antibodies reacting with four different epitopes on the insulin receptor mimicked the effect of insulin on 2-deoxyglucose uptake. These antibodies also stimulated thymidine incorporation, although the maximum stimulation was only ∼ 30% that of insulin. It is concluded that the insulin-like metabolic effects of antibodies involve a mechanism of receptor activation that is independent of autophosphorylation and hence that receptor autophosphorylation is not an essential step in triggering at least some events in the insulin signaling pathway

  1. Anti-tumour effects of antibodies targeting the extracellular cysteine-rich region of the receptor tyrosine kinase EphB4.

    Science.gov (United States)

    Stephenson, Sally-Anne; Douglas, Evelyn L; Mertens-Walker, Inga; Lisle, Jessica E; Maharaj, Mohanan S N; Herington, Adrian C

    2015-04-10

    EphB4 is a membrane-bound receptor tyrosine kinase (RTK) commonly over-produced by many epithelial cancers but with low to no expression in most normal adult tissues. EphB4 over-production promotes ligand-independent signaling pathways that increase cancer cell viability and stimulate migration and invasion. Several studies have shown that normal ligand-dependent signaling is tumour suppressive and therefore novel therapeutics which block the tumour promoting ligand-independent signaling and/or stimulate tumour suppressive ligand-dependent signaling will find application in the treatment of cancer. An EphB4-specific polyclonal antibody, targeting a region of 200 amino acids in the extracellular portion of EphB4, showed potent in vitro anti-cancer effects measured by an increase in apoptosis and a decrease in anchorage independent growth. Peptide exclusion was used to identify the epitope targeted by this antibody within the cysteine-rich region of the EphB4 protein, a sequence defined as a potential ligand interacting interface. Addition of antibody to cancer cells resulted in phosphorylation and subsequent degradation of the EphB4 protein, suggesting a mechanism that is ligand mimetic and tumour suppressive. A monoclonal antibody which specifically targets this identified extracellular epitope of EphB4 significantly reduced breast cancer xenograft growth in vivo confirming that EphB4 is a useful target for ligand-mimicking antibody-based anti-cancer therapies. PMID:25831049

  2. Monoclonal antibodies specific for oncofetal antigen – immature laminin receptor protein: Effects on tumor growth and spread in two murine models

    Science.gov (United States)

    McClintock, Shannon D; Warner, Roscoe L; Ali, Saqib; Chekuri, Apurupa; Dame, Michael K; Attili, Durga; Knibbs, Randall K; Aslam, Muhammad Nadeem; Sinkule, Joseph; Morgan, Alton Charles; Barsoum, Adel; Smith, Lauren B; Beer, David G; Johnson, Kent J; Varani, James

    2015-01-01

    The oncofetal antigen – immature laminin receptor protein (OFA/iLRP) has been linked to metastatic tumor spread for several years. The present study, in which 2 highly-specific, high-affinity OFA/iLRP-reactive mouse monoclonal antibodies were examined for ability to suppress tumor cell growth and metastatic spread in the A20 B-cell leukemia model and the B16 melanoma model, provides the first direct evidence that targeting OFA/iLRP with exogenous antibodies can have therapeutic benefit. While the antibodies were modestly effective at preventing tumor growth at the primary injection site, both antibodies strongly suppressed end-organ tumor formation following intravenous tumor cell injection. Capacity of anti-OFA/iLRP antibodies to suppress tumor spread through the blood in the leukemia model suggests their use as a therapy for individuals with leukemic disease (either for patients in remission or even as part of an induction therapy). The results also suggest use against metastatic spread with solid tumors. PMID:25799942

  3. Effect of anti-mosquito hemolymph antibodies on fecundity and on the infectivity of malarial parasite Plasmodium vivax to Anopheles stephensi (Diptera:Insecta).

    Science.gov (United States)

    Gulia, Monika; Suneja, Amita; Gakhar, Surendra K

    2002-06-01

    Rabbit antibodies to hemolymph antigens (102.5, 101, 100, 96, 88, 80, 64, 55, 43, 29, and 23 kDa) of Anopheles stephensi reduced fecundity as well as viability in An. stephensi. However, ingestion of these antibodies was not associated with a marked effect on the engorgement of mosquitoes but egg laying was significantly delayed. Antisera raised against hemolymph proteins were also used to identify cross reactive antigens/epitopes present in other tissues by Western blotting, as well as by in vivo ELISA. In addition, a significant reduction in oocyst development was also observed in An. stephensi mosquitoes that ingested anti-hemolymph antibodies along with Plasmodium vivax. The results confirmed the feasibility of targeting mosquito antigens as a novel anti-mosquito strategy, as well as confirmed the usefulness of such antigens for the development of a transmission-blocking vaccine. PMID:12195047

  4. Factors associated with anti-human leukocyte antigen antibodies in patients supported with continuous-flow devices and effect on probability of transplant and post-transplant outcomes

    DEFF Research Database (Denmark)

    Alba, Ana C; Tinckam, Kathryn; Foroutan, Farid;

    2015-01-01

    outcomes. METHODS: We included 143 consecutive heart failure patients who received a CF-VAD as a bridge-to-transplant at 3 institutions. Factors associated with post-VAD peak panel reactive antibodies (PRA) among several measurements were identified using multivariable linear regression. A parametric......BACKGROUND: One major disadvantage of ventricular assist device (VAD) therapy is the development of human-leukocyte antigen (HLA) antibodies. We aimed to identify factors associated with HLA antibodies during continuous flow (CF)-VAD support and assess the effect on transplant probability and...... survival model was used to assess transplant waiting time and probability, risk of rejection, and a composite outcome of rejection, graft failure, and death. RESULTS: Thirty-six patients (25%) were female; mean age was 47 ± 13 years. Eighty-one patients (57%) had a pre-VAD PRA of 0%, and 16 were highly...

  5. Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia : Effects of continued penicillin prophylaxis

    NARCIS (Netherlands)

    Bjornson, AB; Falletta, JM; Verter, JI; Buchanan, GR; Miller, ST; Pegelow, CH; Iyer, RV; Johnstone, HS; DeBaun, MR; Wethers, DL; Woods, GM; Holbrook, CT; Becton, DL; Kinney, TR; Reaman, GH; Kalinyak, K; Grossman, NJ; Vichinsky, E; Reid, CD

    1996-01-01

    Objectives: (1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years ski children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses. Study design:

  6. Immune Response to Recombinant Capsid Proteins of Adenovirus in Humans: Antifiber and Anti-Penton Base Antibodies Have a Synergistic Effect on Neutralizing Activity

    Science.gov (United States)

    Gahéry-Ségard, Hanne; Farace, Françoise; Godfrin, Dominique; Gaston, Jesintha; Lengagne, Renée; Tursz, Thomas; Boulanger, Pierre; Guillet, Jean-Gérard

    1998-01-01

    Replication-deficient adenovirus used in humans for gene therapy induces a strong immune response to the vector, resulting in transient recombinant protein expression and the blocking of gene transfer upon a second administration. Therefore, in this study we examined in detail the capsid-specific humoral immune response in sera of patients with lung cancer who had been given one dose of a replication-defective adenovirus. We analyzed the immune response to the three major components of the viral capsid, hexon (Hx), penton base (Pb), and fiber (Fi). A longitudinal study of the humoral response assayed on adenovirus particle-coated enzyme-linked immunosorbent assay plates showed that patients had preexisting immunity to adenovirus prior to the administration of adenovirus–β-gal. The level of the response increased in three patients after adenovirus administration and remained at a maximum after three months. One patient had a strong immune response to adenovirus prior to treatment, and this response was unaffected by adenovirus administration. Sera collected from the patients were assayed for recognition of each individual viral capsid protein to determine more precisely the molecular basis of the humoral immune response. Clear differences existed in the humoral response to the three major components of the viral capsid in serum from humans. Sequential appearance of these antibodies was observed: anti-Fi antibodies appeared first, followed by anti-Pb antibodies and then by anti-Hx antibodies. Moreover, anti-Fi antibodies preferentially recognized the native trimeric form of Fi protein, suggesting that they recognized conformational epitopes. Our results showed that sera with no neutralizing activity contained only anti-Fi antibodies. In contrast, neutralizing activity was only obtained with sera containing anti-Fi and anti-Pb antibodies. More importantly, we showed that anti-native Fi and anti-Pb antibodies had a synergistic effect on neutralization. The

  7. A Bivariate Mixture Model for Natural Antibody Levels to Human Papillomavirus Types 16 and 18: Baseline Estimates for Monitoring the Herd Effects of Immunization

    Science.gov (United States)

    Vink, Margaretha A.; Berkhof, Johannes; van de Kassteele, Jan; van Boven, Michiel; Bogaards, Johannes A.

    2016-01-01

    Post-vaccine monitoring programs for human papillomavirus (HPV) have been introduced in many countries, but HPV serology is still an underutilized tool, partly owing to the weak antibody response to HPV infection. Changes in antibody levels among non-vaccinated individuals could be employed to monitor herd effects of immunization against HPV vaccine types 16 and 18, but inference requires an appropriate statistical model. The authors developed a four-component bivariate mixture model for jointly estimating vaccine-type seroprevalence from correlated antibody responses against HPV16 and -18 infections. This model takes account of the correlation between HPV16 and -18 antibody concentrations within subjects, caused e.g. by heterogeneity in exposure level and immune response. The model was fitted to HPV16 and -18 antibody concentrations as measured by a multiplex immunoassay in a large serological survey (3,875 females) carried out in the Netherlands in 2006/2007, before the introduction of mass immunization. Parameters were estimated by Bayesian analysis. We used the deviance information criterion for model selection; performance of the preferred model was assessed through simulation. Our analysis uncovered elevated antibody concentrations in doubly as compared to singly seropositive individuals, and a strong clustering of HPV16 and -18 seropositivity, particularly around the age of sexual debut. The bivariate model resulted in a more reliable classification of singly and doubly seropositive individuals than achieved by a combination of two univariate models, and suggested a higher pre-vaccine HPV16 seroprevalence than previously estimated. The bivariate mixture model provides valuable baseline estimates of vaccine-type seroprevalence and may prove useful in seroepidemiologic assessment of the herd effects of HPV vaccination. PMID:27537200

  8. A Bivariate Mixture Model for Natural Antibody Levels to Human Papillomavirus Types 16 and 18: Baseline Estimates for Monitoring the Herd Effects of Immunization.

    Science.gov (United States)

    Vink, Margaretha A; Berkhof, Johannes; van de Kassteele, Jan; van Boven, Michiel; Bogaards, Johannes A

    2016-01-01

    Post-vaccine monitoring programs for human papillomavirus (HPV) have been introduced in many countries, but HPV serology is still an underutilized tool, partly owing to the weak antibody response to HPV infection. Changes in antibody levels among non-vaccinated individuals could be employed to monitor herd effects of immunization against HPV vaccine types 16 and 18, but inference requires an appropriate statistical model. The authors developed a four-component bivariate mixture model for jointly estimating vaccine-type seroprevalence from correlated antibody responses against HPV16 and -18 infections. This model takes account of the correlation between HPV16 and -18 antibody concentrations within subjects, caused e.g. by heterogeneity in exposure level and immune response. The model was fitted to HPV16 and -18 antibody concentrations as measured by a multiplex immunoassay in a large serological survey (3,875 females) carried out in the Netherlands in 2006/2007, before the introduction of mass immunization. Parameters were estimated by Bayesian analysis. We used the deviance information criterion for model selection; performance of the preferred model was assessed through simulation. Our analysis uncovered elevated antibody concentrations in doubly as compared to singly seropositive individuals, and a strong clustering of HPV16 and -18 seropositivity, particularly around the age of sexual debut. The bivariate model resulted in a more reliable classification of singly and doubly seropositive individuals than achieved by a combination of two univariate models, and suggested a higher pre-vaccine HPV16 seroprevalence than previously estimated. The bivariate mixture model provides valuable baseline estimates of vaccine-type seroprevalence and may prove useful in seroepidemiologic assessment of the herd effects of HPV vaccination. PMID:27537200

  9. Effects of anti-C23 (nucleolin) antibody on transcription of ribosomal DNA in Chironomus salivary gland cells

    Energy Technology Data Exchange (ETDEWEB)

    Egyhazi, E.; Pigon, A. (Karolinska Institutet, Stockholm (Sweden)); Chang, Jinhong; Ghaffari, S.H.; Dreesen, T.D.; Wellman, S.E.; Case, S.T.; Olson, M.O.J. (Univ. of Mississippi Medical Center, Jackson (USA))

    1988-10-01

    Protein C23 (also called nucleolin or 100-kDa nucleolar protein) is a major nucleolar phosphoprotein involved in ribosome biogenesis. To determine the effects of protein C23 on preribosomal RNA (pre-rRNA) synthesis anti-C23 antiserum was microinjected into nuclei of Chironomus tentans salivary glands. Transcription was measured by incubation of the glands with {sup 32}P-labeled RNA precursors followed by microdissection of nucleoli, RNA extraction, and electrophoretic analyses. Injection of the anti-C23 antibody caused a 2- to 3.5-fold stimulation of {sup 32}P incorporation into 38 S pre-rRNA. No stimulation was observed in salivary glands injected with preimmune serum or antiserum preabsorbed with protein C23. The stimulatory effect was selective for pre-rRNA as indicated by the lack of stimulation of {sup 32}P incorporation into extranucleolar RNA. Injection of the antiserum produced little or no effect on pre-RNA processing as measured by the relative amounts of {sup 32}P-labeled intermediate cleavage products of pre-rRNA in stimulated versus control glands. These results suggest that protein C23 not only is involved in ribosome assembly but also plays a role in regulating the transcription of the preribosomal RNA.

  10. Effects of anti-C23 (nucleolin) antibody on transcription of ribosomal DNA in Chironomus salivary gland cells

    International Nuclear Information System (INIS)

    Protein C23 (also called nucleolin or 100-kDa nucleolar protein) is a major nucleolar phosphoprotein involved in ribosome biogenesis. To determine the effects of protein C23 on preribosomal RNA (pre-rRNA) synthesis anti-C23 antiserum was microinjected into nuclei of Chironomus tentans salivary glands. Transcription was measured by incubation of the glands with 32P-labeled RNA precursors followed by microdissection of nucleoli, RNA extraction, and electrophoretic analyses. Injection of the anti-C23 antibody caused a 2- to 3.5-fold stimulation of 32P incorporation into 38 S pre-rRNA. No stimulation was observed in salivary glands injected with preimmune serum or antiserum preabsorbed with protein C23. The stimulatory effect was selective for pre-rRNA as indicated by the lack of stimulation of 32P incorporation into extranucleolar RNA. Injection of the antiserum produced little or no effect on pre-RNA processing as measured by the relative amounts of 32P-labeled intermediate cleavage products of pre-rRNA in stimulated versus control glands. These results suggest that protein C23 not only is involved in ribosome assembly but also plays a role in regulating the transcription of the preribosomal RNA

  11. Is the treatment effect of IFN-beta restored after the disappearance of neutralizing antibodies?

    DEFF Research Database (Denmark)

    Sorensen, P S; Koch-Henriksen, Nils; Flachs, Esben Meulengracht; Bendtzen, K

    2008-01-01

    comparing the NAb-positive with the NAb-negative periods was 1.98 (95% confidence interval: 1.32-2.97). CONCLUSION: Under NAb-positive periods, the clinical effect of IFN-beta was abolished. When NAbs disappeared spontaneously under continued treatment, patients regained the full effect of INF-beta-1b...

  12. Monoclonal antibodies

    International Nuclear Information System (INIS)

    Monoclonal antibodies (MAbs) are antibodies having single specificity for a given antigen site (epitope). The development of hybridoma technology and the relative ease by which MAbs can be prepared has revolutionized many aspects of serological applications in diagnosis and differentiation of disease producing agents. The property of monospecificity offers advantages in diagnostic applications over polyclonal sera in that tests can be defined exactly with regard to the antigen detected and the affinity of reaction between the given antigenic site and the monoclonal reagent. In addition, MAbs offer better possibilities for test standardization, because the same reagent can be used in different laboratories. Such an MAb can be supplied by a central laboratory or 'grown' from hybridoma cells, ensuring that the resultant product is identical from laboratory to laboratory and that the part of the test involving the MAb reaction is the same. The methodologies for inoculation regimes, mice, cloning methods, selection of fusion partners, etc., have been validated extensively in developed country laboratories. The decision to establish a MAb production facility must be examined on a strict cost-benefit basis, since it is still expensive to produce a product. There are many MAbs available that should be sought to allow exploitation in developing tests. If a production facility is envisaged, it should produce reagents for national needs, i.e. there should be a clear problem oriented approach whereby exact needs are defined. In the field of veterinary applications, MAbs are the central reagent in many immunoassays based on the enzyme linked immunosorbent assay (ELISA). The development of specific tests for diagnosing diseases is dominated by MAbs and has been fuelled by a strong research base, mainly in developed countries allied to developing countries through the study of related diseases. Thus, there are very many assays dependent on MAbs, some of which form the basis of

  13. Study into the effect of 60Co γ-rays on the lymphocyte subests with monoclonal antibodies

    International Nuclear Information System (INIS)

    Three kinds of monoclonal antibodies, OKT4McAb, OKT8McAb and HI43McAb, were used in experiment to identify T helper (Th), T suppresser (Ts) and B lymphocytes respectively. After lymphocytes were exposed to 0.1 Gy, 0.25 Gy, 1 Gy and 4 Gy 60Co γ-rays, immediately, the author observed the radiation effect by means of the indirect immunofluorescence test. 200 cells were conted to obtain the percent of immunofluorescence positive cells. The results indicated that when the Th, Ts and B lymphocytes were irradiated by 0.1 Gy 60Co γ-rays, their abilities to combine with McAb decreased significantly. The radiation effect became more and more obvious with increasing radiation dosage. The percents of three kinds of the immunofluorescence positive cells were analysed with weighted linear regression methods. The correlation coefficients (r) of Th, Ts and B lymphocytes were 0.8131, 0.8832 and 0.9086 respectively. The significant tests of regression coefficient showed that the radiosensitivities of Ts and B lymphocytes had no significant difference and were higher than that of Th lymphocytes

  14. Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison′ s disease with primary hypothyroidism

    Directory of Open Access Journals (Sweden)

    Jaya Prakash Sahoo

    2016-01-01

    Full Text Available Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (22 pmol/L and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical was defined as high thyroid stimulating hormone (TSH with/without low free thyroxine (fT4. TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.

  15. Molecular profiling of signalling proteins for effects induced by the anti-cancer compound GSAO with 400 antibodies

    International Nuclear Information System (INIS)

    GSAO (4-[N-[S-glutathionylacetyl]amino] phenylarsenoxide) is a hydrophilic derivative of the protein tyrosine phosphatase inhibitor phenylarsine oxide (PAO). It inhibits angiogenesis and tumour growth in mouse models and may be evaluated in a phase I clinical trial in the near future. Initial experiments have implicated GSAO in perturbing mitochondrial function. Other molecular effects of GSAO in human cells, for example on the phosphorylation of proteins, are still largely unknown. Peripheral white blood cells (PWBC) from healthy volunteers were isolated and used to profile effects of GSAO vs. a control compound, GSCA. Changes in site-specific phosphorylations, other protein modifications and expression levels of many signalling proteins were analysed using more than 400 different antibodies in Western blots. PWBC were initially cultured in low serum conditions, with the aim to reduce basal protein phosphorylation and to increase detection sensitivity. Under these conditions pleiotropic intracellular signalling protein changes were induced by GSAO. Subsequently, PWBC were cultured in 100% donor serum to reflect more closely in vivo conditions. This eliminated detectable GSAO effects on most, but not all signalling proteins analysed. Activation of the MAP kinase Erk2 was still observed and the paxillin homologue Hic-5 still displayed a major shift in protein mobility upon GSAO-treatment. A GSAO induced change in Hic-5 mobility was also found in endothelial cells, which are thought to be the primary target of GSAO in vivo. Serum conditions greatly influence the molecular activity profile of GSAO in vitro. Low serum culture, which is typically used in experiments analysing protein phosphorylation, is not suitable to study GSAO activity in cells. The signalling proteins affected by GSAO under high serum conditions are candidate surrogate markers for GSAO bioactivity in vivo and can be analysed in future clinical trials. GSAO effects on Hic-5 in endothelial cells may

  16. IGF-1 Antibody Prolongs the Effective Duration Time of Botulinum Toxin in Decreasing Muscle Strength

    Directory of Open Access Journals (Sweden)

    Yuguo Zheng

    2013-04-01

    Full Text Available Botulinum toxin type-A (Btx-A, a powerful therapeutic tool in various medical specialties, requires repeated injections to maintain its effect. Therefore, novel methods to prolong the effective duration time of Btx-A are highly needed. Rats were assigned to three major groups: control group (n = 30, Btx-A group (n = 30, and IGF-1 Ab groups. IGF-1 Ab groups were composed by sub-groups A1–A5 (each has 25 rats for the subsequent IGF-1Ab dose-effect study. Muscle strength was determined by a survey system for rat lower limbs nerve and muscle function. Muscle-specific receptor tyrosine kinase (MuSK, Insulin-like growth factor binding protein-5 (IGFBP5, and growth-associated protein, 43-kDa (GAP43 were determined by real-time polymerase chain reactions (PCRs and Western blot. We found that Btx-A decreased the muscle strength, with a paralysis maintained for 70 days. IGF-1Ab prolonged the effective duration time of Btx-A. Real-time PCRs and Western blot showed that IGF-1Ab delayed the increase of MuSK and IGFBP5 after Btx-A injection, without affecting GAP43. These results indicate that IGF-1Ab might prolong the effective duration time of Btx-A on muscle strength through delaying the increase of MuSK. It would be interesting to determine whether IGF-1Ab can be used as an auxiliary measure to the Btx-A treatment in the future.

  17. Effect of cisplatin alone or combined with monoclonal anti-programmed death ligand-1 anti-body on lung adenocarcinoma cell line SPCA-1 and T lymphocytes

    Institute of Scientific and Technical Information of China (English)

    潘雪

    2014-01-01

    Objective To observe the effect of cisplatin alone or combined with anti-programmed death ligand 1 monoclonal antibody(anti-PD-L1 mA b)on the co-culture system of lung adenocarcinoma SPCA-1 cells and T lymphocytes,and therefore to study the immunotherapeutic effect of anti-PD-L1 mA b on lung cancer.Methods Human adenocarcinoma SPCA-1 cell line was selected by

  18. Effect of Early Antibiotic Treatment on the Antibody Response to Cytoplasmic Proteins of Brucella melitensis in Mice

    OpenAIRE

    Bowden, Raul A.; Racaro, Graciela C.; Baldi, Pablo C.

    1999-01-01

    To test whether antibiotic therapy hampers the antibody response to Brucella antigens, 30 BALB/c mice were infected with Brucella melitensis H38 and randomized for treatment with doxycycline administered intraperitoneally for 42 days starting at 7 or 28 days postinfection (p.i.) (groups DOX7 and DOX28, respectively) or for no treatment (control group). Antibodies to smooth lipopolysaccharide (LPS) reached peak levels (mean optical density [OD] = 2.618) between days...

  19. The Effect of Prophylactic Antipyretic Administration on Post-Vaccination Adverse Reactions and Antibody Response in Children: A Systematic Review

    OpenAIRE

    Rashmi Ranjan Das; Inusha Panigrahi; Sushree Samiksha Naik

    2014-01-01

    Background Prophylactic antipyretic administration decreases the post-vaccination adverse reactions. Recent study finds that they may also decrease the antibody responses to several vaccine antigens. This systematic review aimed to assess the evidence for a relationship between prophylactic antipyretic administration, post-vaccination adverse events, and antibody response in children. Methods A systematic search of major databases including MEDLINE and EMBASE was carried out till March 2014. ...

  20. Monoclonal antibodies.

    Science.gov (United States)

    2009-01-01

    The ability to produce and exploit monoclonal antibodies (mAbs) has revolutionized many areas of biological sciences. The unique property of an mAb is that it is a single species of immunoglobulin (IG) molecule. This means that the specificity of the interaction of the paratopes on the IG, with the epitopes on an antigenic target, is the same on every molecule. This property can be used to great benefit in immunoassays to provide tests of defined specificity and sensitivity, which improve the possibilities of standardization. The performance of assays can often be determined relating the actual weight of antibody (hence the number of molecules) to the activity. Often the production of an mAb against a specific epitope is the only way that biological entities can be differentiated. This chapter outlines the areas involving the development of assays based on mAbs. The problems involved address include the physical aspects of mAbs and how they may affect assay design and also the implications of results based on monospecific reagents. Often these are not fully understood, leading to assays that are less than satisfactory, which does not justify the relatively high cost of preparing and screening of mAbs. There are many textbooks and reviews dealing with the preparation of mAbs, the principles involved, and various purification and manipulative methods for the preparation of fragments and conjugation. There has been little general information attempting to summarize the best approaches to assay design using mAbs. Much time can be wasted through bad planning, and this is particularly relevant to mAbs. A proper understanding of some basic principles is essential. It is beyond the scope of this chapter to discuss all aspects, but major areas are highlighted. PMID:19219589

  1. Effect of Early Antibiotic Treatment on the Antibody Response to Cytoplasmic Proteins of Brucella melitensis in Mice

    Science.gov (United States)

    Bowden, Raul A.; Racaro, Graciela C.; Baldi, Pablo C.

    1999-01-01

    To test whether antibiotic therapy hampers the antibody response to Brucella antigens, 30 BALB/c mice were infected with Brucella melitensis H38 and randomized for treatment with doxycycline administered intraperitoneally for 42 days starting at 7 or 28 days postinfection (p.i.) (groups DOX7 and DOX28, respectively) or for no treatment (control group). Antibodies to smooth lipopolysaccharide (LPS) reached peak levels (mean optical density [OD] = 2.618) between days 56 and 70 p.i. in the control group, and similar peak levels (mean OD = 2.486) were observed in the DOX28 group, but significantly lower peak levels (mean OD = 0.821) were observed at 28 days p.i. in the DOX7 group. The antibody response against cytoplasmic proteins depleted of LPS (CPs) reached maximal levels (mean OD = 2.402) between days 56 and 70 p.i. in the control group, but no response was detected in the DOX7 group. Anti-CP antibodies were detected in only three animals from the DOX28 group, at levels significantly lower than those in the control group (mean maximal OD = 0.791). The pattern of antibody response to an 18-kDa cytoplasmic protein of Brucella spp. was similar to that against the CP antigen. This study shows that early antibiotic treatment affects the antibody response of mice to cytoplasmic proteins of Brucella and, to a lesser extent, to LPS. PMID:10225853

  2. Effects of Anti-CD45RB Monoclonal Antibody for T Lymphocyte Subsets in Mice Heart Transplantation Model.

    Science.gov (United States)

    Deng, C-Y; Wang, X-F; Qi, H; Li, F-R

    2016-08-01

    Anti-CD45RB monoclonal antibody (anti-CD45RBmAb), as a new immune tolerance inducer, may inhibit T cell proliferation and induce immune tolerance through competitive combination with CD45RB on the T cell surface, which blocks the conduction of activation signals. However, how anti-CD45RBmAb plays its role on T lymphocyte subsets during immunosuppression remains unclear. In this work, we investigate the effects of anti-CD45RBmAb on CD3(+) T lymphocyte both in vitro and in allogeneic heart transplant model in vivo. Interestingly, anti-CD45RBmAb could inhibit the proliferation of T cells, promote the transformation of T lymphocyte to Treg and Th2 cells, suppress the transformation to Th17 and Th1 cells, increase the number of Ts cells, decrease the number of Tm cells and thus play a role in immune inhibition and induction of immune tolerance. PMID:27146476

  3. Effects of dopamine concentration on energy transfer between dendrimer-QD and dye-labeled antibody

    International Nuclear Information System (INIS)

    The Unified Parkinson's Disease Rating Scale (UPDRS) is currently used to assess Parkinson's disease, and is a key method for determining the progression of disease based on the gross findings of patients. However, this method cannot quantify the extent of disease of patients, which means the administration of drugs cannot be determined on a real-time basis. Thalamotomy also causes discomfort and pain to the patients, and adversely affects treatment as it is performed following the onset of symptoms. Accordingly, the dopamine concentration, which is one of the key factors in determining this disease, needs to be detected quantitatively at ordinary times. Hence, the development of a bio-kit or a bio-sensor is essential for effectively prescribing the correct dopamine concentration in a customizable manner. In this study, the effect of dopamine level on this phenomenon was observed using the Forster resonance energy transfer (FRET) phenomenon generated between a donor and acceptor. By confirming the photoluminescence (PL) and lifetime data, it was demonstrated that the degree of energy transfer increased with increasing dopamine concentration. To apply this phenomenon to an optical sensor, a glass surface was modified with a quantum dot (QD)-encapsulated dendrimer, and analyzed using the contact angle and ATR-FTIR. The topology of surface was determined by an atomic force microscope (AFM).

  4. Mutual boosting effects of sensitization with timothy grass pollen and latex glove extract on IgE antibody responses in a mouse model.

    Science.gov (United States)

    Mahler, V; Diepgen, T L; Kubeta, O; Leakakos, T; Truscott, W; Schuler, G; Kraft, D; Valenta, R

    2000-05-01

    Type I allergy to natural rubber latex can be an important health problem for latex-exposed individuals (e.g., health care workers, spina bifida children). Also beyond these risk groups, a high sensitization rate of varying and partly unknown clinical relevance has been reported. Atopy represents a risk factor for latex allergy and recent studies indicate that patients suffering from pollen allergies may have pollen allergen-specific IgE antibodies which cross-react with latex allergens. In order to investigate whether sensitization to pollen allergens can have priming effects on the production of IgE antibodies against latex in vivo, a mouse model was established. Groups of 10 BALB/C mice were immunized with Al(OH)3-adsorbed pollen extracts from timothy grass, ragweed, mugwort, or birch. For control purposes, one additional group received adjuvant only and another group was not immunized. Half of the mice of each group were subsequently immunized with Al(OH)3-adsorbed latex glove extract, the other half with adjuvant only. Pollen and latex-specific IgE- and IgG1-antibody responses were analyzed by enzyme-linked immunosorbent assay and statistically evaluated by analysis of variance. Antibody responses to cross-reactive antigens were investigated by immunoblotting. We found significantly increased IgE reactivities to latex after pollen sensitization and vice versa. Moreover, mice immunized with timothy grass pollen extract alone - without subsequent latex immunization - displayed IgE reactivity to latex. Cross-reactive antibodies were directed against pollen antigens of approximately 60 kDa molecular weight. Our results thus demonstrate a mutual boosting effect of pollen and latex sensitization in vivo which may be also operative in polysensitized plant allergic patients. PMID:10771489

  5. A simple and cost-effective method for rapid purification of alkyl hydroperoxide reductase (AhpC from Helicobacter pylori and its antibody production

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available Background and the purpose of the study: Helicobacter pylori express abundant amounts of AhpC enzyme that functions to reduce organic hydroperoxides (ROOH into the corresponding non-toxic alcohols (ROH. This conserved antigen has been earlier described as specific and unique for H. pylori and therefore, both H. pylori AhpC and Anti-AhpC could be useful in the development of serologic and stool antigen tests, to detecting and monitoring H. pylori infection. AhpC may also serves as a potential target for an antimicrobial agent or for vaccine development. The aim of this study was to simplify isolation and purification of the AhpC and production of a highly specific polyclonal antibody against it. Methods and Results: In this paper a simple method was used for protein purification and antibody production which avoids both the long term AhpC protein purification procedure and the addition of Freund's adjuvant. One-dimensional preparative gel electrophoresis allows a single and short purification step and the high resolution capacity of this technique leads to a high level of purity of the protein and consequently to a very high specificity of the antibody. Moreover, it avoids contamination by other non-specific proteins which often appear during protein purification by column chromatographic techniques. Major Conclusion: The present method is simple, rapid and cost-effective and makes it possible to produce antibody for stool antigen enzyme immunoassay in short time and at low cost.

  6. Effect of protein kinase inhibitors on primary antibody induction in tissue cultures.

    Science.gov (United States)

    Sterzl, J; Milerová, J; Votruba, J; Sterzl, I

    1998-10-01

    The effects of protein-kinase-inhibitors (PKIs) on protein kinase C (PKCs) i.e., staurosporin, calphostin C, H-7, H-8, H-9, on phosphatidyl inositol 3-proteinkinase (PI3-K) i.e., wortmannin, and on protein tyrosine kinase (PTKs) i.e., genistein, herbimycin A, sanguinarin, lavendustin A and B were tested on the induction phase of the primary Ab-response in vitro. The inhibitory action of PKIs was the highest with herbimycin A, sanguinarin, H-9 and wortmannin. Although wortmannin inhibits the function of T-lymphocytes (Taub et al., 1997, Shi et al., 1997), we believe that this communication is the first report of PKIs immunosuppressive action on the inductive steps of Ab-formation. PMID:9839662

  7. The effect of olive oil polyphenols on antibodies against oxidized LDL. A randomized clinical trial

    DEFF Research Database (Denmark)

    Castañer, Olga; Fitó, Montserrat; López-Sabater, M Carmen; Poulsen, Henrik E; Nyyssönen, Kristiina; Salonen, Jukka T; De la Torre-Carbot, Karina; Zunft, Hans-Franz; De la Torre, Rafael; Bäumler, Hans; Gaddi, Antonio V; Saez, Guillermo T; Tomás, Marta; Covas, Maria-Isabel; Schröder, Helmut

    2011-01-01

    of oxLDL to autoantibody generation. METHODS: In a crossover, controlled trial, 200 healthy men were randomly assigned to 3-week sequences of 25 mL/day of 3 olive oils with high (366 mg/kg), medium (164 mg/kg), and low (2.7 mg/kg) phenolic content. RESULTS: Plasma OLAB concentration was inversely......BACKGROUND & AIM: Oxidized LDL (oxLDL) is a highly immunogenic particle that plays a key role in the development of atherosclerosis. Some data suggest a protective role of OxLDL autoantibodies (OLAB) in atherosclerosis. Our aim was to assess the effect of olive oil polyphenols on the immunogenicity...

  8. Effects of aflatoxin B1 and fumonisin B1 on body weight, antibody titres and histology of broiler chicks.

    Science.gov (United States)

    Tessari, E N C; Oliveira, C A F; Cardoso, A L S P; Ledoux, D R; Rottinghaus, G E

    2006-06-01

    1. Our objective was to evaluate the toxic effects of aflatoxin B1 (AFB1) and fumonisin B1 (FB1), administered singly or in combination to broilers. 2. Feeds were prepared with concentrations equal to 0, 50 and 200 microg AFB1/kg, and/or 0, 50 and 200 mg FB1/kg, and offered to broiler chicks from 8 to 41 d of age. The experimental design was totally randomised, in a 3 x 3 factorial arrangement with 9 treatments and 12 birds per treatment. Animals were vaccinated against Newcastle disease on d 14 of life and killed at 41 d. 3. Compared with controls, all mycotoxin-treated groups at 41 d had lower body weight and weight gain, and higher relative heart weight. The relative weight of the liver increased only in birds fed diets containing 200 mg FB1, singly or in combination with AFB1. 4. At 35 d, all groups receiving mycotoxin-treated rations had reduced geometrical mean antibody titres, with birds from groups fed combinations of AFB1 and FB1/kg having even lower values, when compared to the other groups. 5. Histological changes were observed only in liver from birds fed mycotoxin-contaminated rations, and in kidneys of birds fed the diet containing 200 microg AFB1 and 200 mg FB1/kg. Main alterations included vacuolar degeneration and cell proliferation of bile ducts in the liver, and hydropic degeneration in renal tubules in the kidneys. 6. We concluded that AFB1 and FB1 in combination have primarily additive effects on body weight, liver structure and immunological response of broilers at the concentrations used. PMID:16787861

  9. Effect of antilymphoma antibody, 131I-Lym-1, on peripheral blood lymphocytes in patients with non-Hodgkin's lymphoma.

    Science.gov (United States)

    Schillaci, Orazio; DeNardo, Gerald L; DeNardo, Sally J; Goldstein, Desiree S; Kroger, Linda A; O'Donnell, Robert T; Lamborn, Kathleen R

    2007-08-01

    Anti-CD20 monoclonal antibodies (mAbs), unlabeled rituximab (Rituxan, Biogen Idec Inc., Cambridge, MA; and Genentech Inc., South San Francisco, CA) or radiolabeled 90Y-ibritumomab (Zevalin, Biogen Idec Inc., Cambridge, MA) and 131I-tositumomab (Bexxar; Glaxo Smith Kline, Research Triangle Park, NC), have proven to be effective therapy for non-Hodgkin's lymphoma (NHL), but also induce immediate and persistent decreases in normal peripheral blood lymphocytes (PBLs). Lym-1, a mAb that selectively targets malignant lymphocytes, also has induced therapeutic responses and prolonged survival in patients with NHL when labeled with iodine-131 (131I). We have retrospectively examined its effect on PBLs in 41 NHL patients that had received 131I-Lym-1 therapy. Absolute lymphocyte counts (ALCs) were evaluated before and after the first and last 131I-Lym-1 infusion. Modest decreases in PBLs were observed in most of the patients. Using strict criteria to define recovery, time to recovery was determined for 19 patients, with the remainder censored because of insufficient follow-up (median follow up for censored patients: 22 days). Using Kaplan-Meier estimates, it would be predicted that 31% of patients would recover by 28 days and that median time to recovery would be 44 days after the last 131I-Lym-1 infusion. No predictors were found for time to recovery, considering such factors as the administered Lym-1 or 131I dose, spleen volume, or radiation doses to the body, marrow, or spleen. The data suggest that the effect of 131I-Lym-1 on ALC is the result of a nonspecific radiation effect, rather than a specific Lym-1 mAb effect. The shorter time required for ALC recovery after 131I-Lym-1 when compared to that reported for anti-CD20 mAbs, whether radiolabeled or otherwise, is probably related to differing mechanisms for lymphocytotoxicity and lesser Lym-1 antigenic density on normal B-lymphocytes. PMID:17803447

  10. Effects of supplemental chromium on antibody responses of newly weaned feedlot calves to immunization with infectious bovine rhinotracheitis and parainfluenza 3 virus.

    OpenAIRE

    Burton, J. L.; Mallard, B A; Mowat, D N

    1994-01-01

    The objective of this study was to determine the effect of supplemental dietary chromium (Cr) on antibody responses of feedlot calves. Fifty-five newly weaned calves were divided into two groups, 28 that received supplemental Cr and 27 that did not, and were immunized with a commercial vaccine against bovine infectious rhinotracheitis virus (IBR) and bovine parainfluenza virus type 3(PI-3). Sera harvested from blood sampled preimmunization, and at days 14 and 28 postimmunization (PI), were as...

  11. The Effects of Anti-insulin Antibodies and Cross-reactivity with Human Recombinant Insulin Analogues in the E170 Insulin Immunometric Assay

    OpenAIRE

    Kim, Serim; Yun, Yeo Min; Hur, Mina; Moon, Hee Won; Kim, Jin Q

    2011-01-01

    Background Insulin assays are affected by varying degrees of interference from anti-insulin antibodies (IAs) and by cross-reactivity with recombinant insulin analogues. We evaluated the usefulness of the E170 insulin assay by assessing IA effects and cross-reactivity with 2 analogues. Methods Sera were obtained from 59 type 2 diabetes patients receiving continuous subcutaneous insulin infusion and 18 healthy controls. Insulin levels were determined using an E170 analyzer. To investigate the e...

  12. Effects of Thyroid Peroxidase Antibody on Maternal and Neonatal Outcomes in Pregnant Women in an Iodine-Sufficient Area in China

    OpenAIRE

    Xi Chen; Bai Jin; Jun Xia; Xincheng Tao; Xiaoping Huang; Lu Sun; Qingxin Yuan

    2016-01-01

    Purposes. To evaluate the effects of thyroid peroxidase antibodies (TPOAb) on maternal and neonatal adverse outcomes in pregnant women. Methods. 208 pregnant women at 24–28 weeks were divided into two groups, TPOAb-positive and TPOAb-negative groups. Thyroid function and TPOAb were determined in all subjects until 12 months postpartum. Levothyroxine was supplemented to maintain euthyroid with periodical checking of thyroid functions. The prevalence of postpartum thyroiditis (PPT), placenta pr...

  13. Effect of monoclonal antibodies to early pregnancy factor (EPF) on the in vivo growth of transplantable murine tumours.

    Science.gov (United States)

    Quinn, K A; Morton, H

    1992-01-01

    Neutralisation studies with monoclonal antibodies (mAbs) specific for early pregnancy factor (EPF) have shown it to be essential for the continuation of pregnancy in mice and the growth of some tumour cells in vitro. These studies report that the mAbs are also able to limit the growth of two murine tumour lines transplanted s.c. The development of MCA-2 tumours in CBA mice was unaffected by the injection of 1 mg anti-EPF IgM at the time of tumour cell inoculation. However, four doses of 500 micrograms anti-EPF, injected one dose per day for 4 days after tumour cell inoculation, significantly retarded tumour development such that no tumours were palpable on day 13. A similar dose regimen of control IgM had no effect on tumour size. Dose/response studies revealed that lower doses of anti-EPF administered after tumour cell inoculation were effective in retarding the growth of the MCA-2 tumours. The effects of anti-EPF mAb administration on the growth rate of palpable B16 tumours established s.c. in C57BL/6 mice was also determined. Tumours injected with 6 mg anti-EPF 5/341 or anti-EPF 5/333 mAbs showed significant decrease in the uptake of [3H]thymidine into tumour tissue, measured 16 h after injection. Furthermore, titration of sera for active EPF showed that a significant reduction in the EPF titre was associated with a significant inhibition of tumour DNA synthesis. Thus it appears that neutralisation of EPF retards tumour growth both in vitro and in vivo. In vitro the effects must be due to anti-EPF mAb interfering with a direct mechanism that contributes to the maintenance of cells in the active growing phase. However, in vivo host immunological mechanism that are modified to allow tumour survival may also be affected. The presence of EPF-induced suppressor factor circulating in the serum of tumour-bearing mice has been confirmed and the contribution of such factors to tumour progression must now be investigated. PMID:1537058

  14. Effects of saffron (Crocus sativus petal ethanolic extract on hematology, antibody response, and spleen histology in rats

    Directory of Open Access Journals (Sweden)

    Atefeh Babaei

    2014-02-01

    Full Text Available Objective: Saffron petal is a by-product that contains flavonoids and anthocyanins. In order to study the effects of saffron petal extract (SPE on blood parameters, immune system, and spleen histology, five treatments (n=6 were used in a completely randomized design. Materials and Methods: The treatments were 0, 75, 150, 225, and 450 mg/kg body weight of SPE. The SPE was injected intraperitoneally to 30 rats (10-week old, weighing 225±15 g for 14 days. Immunization was performed using 1×108 sheep red blood cells (SRBC on days 0 and 7 subcutaneously in all treatment groups. On day 15, blood was collected from the heart of rats after anesthesia. One part of samples were poured in heparinized tubes for counting whole blood cells (CBC and different white blood cells (WBC and the other part was used to measure IgG using ELISA technique. The spleen was stained by hematoxylin- eosin for histological study. The data were statistically analyzed using ANOVA program and the means evaluation was done using Tukey’s test. Results are presented as mean±SD. Results: Results showed no significant difference between treatments and control group regarding the amount of RBC, HGB, HCT, and PLT. The level of IgG at 75 mg/kg was significantly increased in comparison with other groups. No changes were observed in spleen histology. Conclusion: The results indicate that use of SPE at dose of 75 mg/kg causes an increase in antibody response without any change in hematological parameters and spleen histology.

  15. Effects of the Sheep Polyclonal Antibodies Against the Porcine Adipocyte Plasma Membrane Proteins on Porcine Carcass Composition and Meat Quality

    Institute of Scientific and Technical Information of China (English)

    GAO Shi-zheng; HU Hong-mei; LIU Ling-yun; ZHANG Xi; LIU Yong-gang; GE Chang-rong

    2007-01-01

    To detect the effects of the polyclonal antibodies raised in sheep against porcine adipocyte plasma membranes on the porcine carcass composition and meat quality, 30 pigs assigned into 6 treatment groups were given intraperitoneal injections of sheep antipig adipocyte plasma membrane immunoglobulin (ASIg) or sheep nonimmune serum immunoglobulin (NSIg). At the end of the experiment, the pigs were slaughtered at 90 kg body weight, and carcasses and meat quality were evaluated. The results showed that when pigs intraperitoneally immunized with 20 or 30 mg ASIg at 15 kg body weight, 20 mg purified ASIg twice at 15 and 60 kg body weight, or 20 mg purified ASIg at 60 kg body weight, respectively, their lean meat percentage, fat meat percentage, backfat thickness, loin eye area leaf fat weight, caul fat weight, heart weight, liver weight, and kidney weight were significantly affected. However, the kidney weight, lung weight, dressing percentage,and spleen weight did not remarkably change. Our results indicated that pigs intraperitoneally immunized with 20 or 30 mg ASIg at 15 kg body weight, and 20 mg ASIg twice at 15 and 60 kg body weight, have significantly different drip loss rate,cooked meat ratio, tenderness, storage loss rate, muscle fiber diameter, moisture content, dry matter content, crude protein content, and crude fat content from the control group that received 20 mg NSIg at 15 kg body weight. However, meat pH,meat color value, meat marbling score, inosinate, and myohemoglobin were not significantly affected. Our results indicated ASIg could not significantly affect the content of most muscular amino acids and intramuscular fatty acids.

  16. Negative effects of a disulfide bond mismatch in anti-rabies G protein single-chain antibody variable fragment FV57.

    Science.gov (United States)

    Duan, Ye; Gu, Tiejun; Zhang, Xizhen; Jiang, Chunlai; Yuan, Ruosen; Li, Zhuang; Wang, Dandan; Chen, Xiaoxu; Wu, Chunlai; Chen, Yan; Wu, Yongge; Kong, Wei

    2014-06-01

    Rabies virus (RV) causes a fatal infectious disease requiring efficient post-exposure prophylaxis (PEP), which includes a rabies vaccine and rabies immunoglobulin (RIG). The single-chain antibody variable fragment (scFv), a small engineered antibody fragment derived from an antibody variable heavy chain and light chain, has the potential to replace the current application of RIG. In previous studies, we constructed and evaluated an anti-rabies virus G protein scFv (FV57) based on the monoclonal antibody CR57. Of the five cysteines in FV57, four are linked in intra-chain disulfide bonds (Cys-VH28/Cys-VH98 and Cys-VL16/Cys-VL84), and one is free (Cys-VL85). However, the thiol in Cys-VL85 neighboring Cys-VL84 in the CDR3 of the light chain is likely to mismatch with the thiol in Cys-VL16 during the renaturing process. In order to study effects of the mismatched disulfide bond, Cys-VL85 and Cys-VL84 of FV57 were mutated to serine to construct mutants FV57(VL85S) and FV57(VL84S). Furthermore, the disulfide bonds in the light chain of FV57, FV57(VL85S) and FV57(VL84S) were deleted by mutating Cys-VL16 to serine. All mutants were prepared and evaluated along with the original FV57. The results indicated that the mismatched disulfide bond of FV57 linking the light chain FR1 and CDR3 would confer deleterious negative effects on its activity against RV, likely due to spatial hindrance in the light chain CDR3. Moreover, avoidance of the disulfide bond mismatch provided an additional 30% protective efficacy against RV infection in the mouse RV challenge model. Thus, modifications of FV57 to eliminate the disulfide bond mismatch may provide a candidate therapeutic agent for effective PEP against rabies. PMID:24598312

  17. Effects of a Proline Endopeptidase on the Detection and Quantitation of Gluten by Antibody-Based Methods during the Fermentation of a Model Sorghum Beer.

    Science.gov (United States)

    Panda, Rakhi; Fiedler, Katherine L; Cho, Chung Y; Cheng, Raymond; Stutts, Whitney L; Jackson, Lauren S; Garber, Eric A E

    2015-12-01

    The effectiveness of a proline endopeptidase (PEP) in hydrolyzing gluten and its putative immunopathogenic sequences was examined using antibody-based methods and mass spectrometry (MS). Based on the results of the antibody-based methods, fermentation of wheat gluten containing sorghum beer resulted in a reduction in the detectable gluten concentration. The addition of PEP further reduced the gluten concentration. Only one sandwich ELISA was able to detect the apparent low levels of gluten present in the beers. A competitive ELISA using a pepsin-trypsin hydrolysate calibrant was unreliable because the peptide profiles of the beers were inconsistent with that of the hydrolysate calibrant. Analysis by MS indicated that PEP enhanced the loss of a fragment of an immunopathogenic 33-mer peptide in the beer. However, Western blot results indicated partial resistance of the high molecular weight (HMW) glutenins to the action of PEP, questioning the ability of PEP in digesting all immunopathogenic sequences present in gluten. PMID:26548701

  18. The effect of prophylaxis with chloroquine and proguanil on delayed-type hypersensitivity and antibody production following vaccination with diphtheria, tetanus, polio, and pneumococcal vaccines

    DEFF Research Database (Denmark)

    Gyhrs, A; Pedersen, B K; Bygbjerg, I;

    1991-01-01

    diphosphate (1,000 mg/week), or 4) proguanil hydrochloride (200 mg/day) for six weeks. Skin testing was performed on days 0 and 28. Vaccinations with diphtheria, tetanus, polio, and pneumococcal polysaccharide antigen vaccines were performed on day 28, and the presence of specific antibodies was determined on...... days 0, 28, and 42. The skin tests induced a significant increase in skin reactive areas from day 0 to day 28 in all groups. Furthermore, the skin test induced an increase in the level of specific IgG for diphtheria and tetanus, but had no effect on antibodies to antigens not included in the skin test...... chemoprophylactic dosages, does not induce any detectable suppression of delayed-type hypersensitivity or vaccination responses to diphtheria, tetanus, polio, or pneumococcal polysaccharide antigens....

  19. Assessment of placental transfer and the effect on embryo-fetal development of a humanized monoclonal antibody targeting lymphotoxin-alpha in non-human primates.

    Science.gov (United States)

    Wang, Hong; Schuetz, Chris; Arima, Akihiro; Chihaya, Yutaka; Weinbauer, Gerhard F; Habermann, Gunnar; Xiao, Jim; Woods, Cynthia; Grogan, Jane; Gelzleichter, Thomas; Cain, Gary

    2016-08-01

    An enhanced embryo-fetal development study was conducted in cynomolgus monkeys using pateclizumab, a humanized IgG1 monoclonal antibody (mAb) targeting lymphotoxin-alpha. Pateclizumab administration between gestation days (GD) 20 and 132 did not induce maternal or developmental toxicities. The ratio of fetal-to-maternal serum concentration of pateclizumab was 0.73% on GD 50 and 61% by GD 139. Decreased fetal inguinal lymph node-to-body weight ratio was present in the high-dose group without microscopic abnormalities, a change attributable to inhibition of lymphocyte recruitment, which is a pharmacologic effect of pateclizumab during late lymph node development. The effect was observed in inguinal but not submandibular or mesenteric lymph nodes; this was attributed to differential susceptibility related to sequential lymph node development. Placental transfer of therapeutic IgG1 antibodies; thus, begins during the first trimester in non-human primates. Depending on the potency and dose levels administered, antibody levels in the fetus may be pharmacologically or toxicologically relevant. PMID:27211603

  20. Antibody therapy for Ebola

    Science.gov (United States)

    Qiu, Xiangguo; Kobinger, Gary P

    2014-01-01

    Ebola viruses can cause severe hemorrhagic fever in humans and nonhuman primates with fatality rates up to 90%, and are identified as biosafety level 4 pathogens and CDC Category A Agents of Bioterrorism. To date, there are no approved therapies and vaccines available to treat these infections. Antibody therapy was estimated to be an effective and powerful treatment strategy against infectious pathogens in the late 19th, early 20th centuries but has fallen short to meet expectations to widely combat infectious diseases. Passive immunization for Ebola virus was successful in 2012, after over 15 years of failed attempts leading to skepticism that the approach would ever be of potential benefit. Currently, monoclonal antibody (mAbs)-based therapies are the most efficient at reversing the progression of a lethal Ebola virus infection in nonhuman primates, which recapitulate the human disease with the highest similarity. Novel combinations of mAbs can even fully cure lethally infected animals after clinical symptoms and circulating virus have been detected, days into the infection. These new developments have reopened the door for using antibody-based therapies for filovirus infections. Furthermore, they are reigniting hope that these strategies will contribute to better control the spread of other infectious agents and provide new tools against infectious diseases. PMID:24503566

  1. Advances in monoclonal antibody application in myocarditis

    Institute of Scientific and Technical Information of China (English)

    Li-na HAN; Shuang HE; Yu-tang WANG; Li-ming YANG; Si-yu LIU; Ting ZHANG

    2013-01-01

    Monoclonal antibodies have become a part of daily preparation technologies in many laboratories.Attempts have been made to apply monoclonal antibodies to open a new train of thought for clinical treatments of autoimmune diseases,inflammatory diseases,cancer,and other immune-associated diseases.This paper is a prospective review to anticipate that monoclonal antibody application in the treatment of myocarditis,an inflammatory disease of the heart,could be a novel approach in the future.In order to better understand the current state of the art in monoclonal antibody techniques and advance applications in myocarditis,we,through a significant amount of literature research both domestic and abroad,developed a systematic elaboration of monoclonal antibodies,pathogenesis of myocarditis,and application of monoclonal antibodies in myocarditis.This paper presents review of the literature of some therapeutic aspects of monoclonal antibodies in myocarditis and dilated cardiomyopathy to demonstrate the advance of monoclonal antibody application in myocarditis and a strong anticipation that monoclonal antibody application may supply an effective therapeutic approach to relieve the severity of myocarditis in the future.Under conventional therapy,myocarditis is typically associated with congestive heart failure as a progressive outcome,indicating the need for alternative therapeutic strategies to improve long-term results.Reviewing some therapeutic aspects of monoclonal antibodies in myocarditis,we recently found that monoclonal antibodies with high purity and strong specificity can accurately act on target and achieve definite progress in the treatment of viral myocarditis in rat model and may meet the need above.However,several issues remain.The technology on howto make a higher homologous and weak immunogenic humanized or human source antibody and the treatment mechanism of monoclonal antibodies may provide solutions for these open issues.If we are to further stimulate

  2. Antibodies and Selection of Monoclonal Antibodies.

    Science.gov (United States)

    Hanack, Katja; Messerschmidt, Katrin; Listek, Martin

    2016-01-01

    Monoclonal antibodies are universal binding molecules with a high specificity for their target and are indispensable tools in research, diagnostics and therapy. The biotechnological generation of monoclonal antibodies was enabled by the hybridoma technology published in 1975 by Köhler and Milstein. Today monoclonal antibodies are used in a variety of applications as flow cytometry, magnetic cell sorting, immunoassays or therapeutic approaches. First step of the generation process is the immunization of the organism with appropriate antigen. After a positive immune response the spleen cells are isolated and fused with myeloma cells in order to generate stable, long-living antibody-producing cell lines - hybridoma cells. In the subsequent identification step the culture supernatants of all hybridoma cells are screened weekly for the production of the antibody of interest. Hybridoma cells producing the antibody of interest are cloned by limited dilution till a monoclonal hybridoma is found. This is a very time-consuming and laborious process and therefore different selection strategies were developed since 1975 in order to facilitate the generation of monoclonal antibodies. Apart from common automation of pipetting processes and ELISA testing there are some promising approaches to select the right monoclonal antibody very early in the process to reduce time and effort of the generation. In this chapter different selection strategies for antibody-producing hybridoma cells are presented and analysed regarding to their benefits compared to conventional limited dilution technology. PMID:27236550

  3. Effects of mutation at the D-JH junction on affinity, specificity, and idiotypy of anti-progesterone antibody DB3

    OpenAIRE

    He, Mingyue; Hamon, Maureen; Liu, Hong; Corper, Adam L.; Michael J. Taussig

    2006-01-01

    The crystal structures of the Fab′ fragment of the anti-progesterone monoclonal antibody DB3 and its complexes with steroid haptens have shown that the D-JH junctional residue TrpH100 is a key contributor to binding site interactions with ligands. The indole group of TrpH100 also undergoes a significant conformational change between the bound and unliganded states, effectively opening and closing the combining site pocket. In order to explore the effect of substitutions at this position on st...

  4. Avian Diagnostic and Therapeutic Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  5. The effect of circulating antigen on the biodistribution of the engineered human antibody hCTM01 in a nude mice model

    International Nuclear Information System (INIS)

    Clinical studies are currently underway to assess the biodistribution and therapeutic potential of the genetically engineered human antibody hCTM01 directed against polymorphic epithelial mucin (PEM) in patients with ovarian carcinoma. The present study was undertaken to assess the effect of circulating PEM antigen on the biodistribution of the anti-PEM antibody in mice bearing MUC-1 transfected adenocarcinoma cell lines. Tumour xenografts were established from three cell lines: 413-BCR, which expressed antigen on the cell surface and also shed antigen into the circulation, E3P23, which expressed the antigen but did not shed into the circulation, and a negative control (410.4 MUCI). Groups of five mice were injected with 1.0 mg/kg antibody, imaged after 72 h and then sacrificed, followed by assay of tissue uptake. The results showed a clear difference in the tumour and liver uptake, with the non-secreting cell line showing almost twice the tumour uptake and approximately 20% of the liver uptake of the secreting cell line. (orig.). With 4 figs., 1 tab

  6. Generation and antitumor effects of an engineered and energized fusion protein VL-LDP-AE composed of single-domain antibody and lidamycin.

    Science.gov (United States)

    Miao, QingFang; Shang, BoYang; Ouyang, ZhiGang; Liu, XiaoYun; Zhen, YongSu

    2007-08-01

    Type IV collagenase plays a pivotal role in invasion, metastasis and angiogenesis of tumor. Single domain antibodies are attractive as tumor-targeting vehicle because of their much smaller size compared with antibody molecules produced by conventional methods. Lidamycin (LDM) is a potent enediyne-containing antitumor antibiotic. In this study an engineered and energized fusion protein VL-LDP-AE composed of lidamycin and VL domain of mAb 3G11 directed against type IV collagenase was prepared using a novel two-step method. First a VL-LDP fusion protein was constructed by DNA recombination. Secondly VL-LDP-AE was obtained by molecular reconstitution. In MTT assay, VL-LDP-AE showed potent cytotoxicity to HT-1080 cells and KB cells with IC(50) values of 8.55 x 10(-12) and 1.70 x 10(-11) mol/L, respectively. VL-LDP-AE showed antiangiogenic activity in chick chrorioallantoic membrane (CAM) assay and tube formation assay. In in vivo experiments, VL-LDP-AE was proved to be more effective than free LDM against the growth of subcutaneously transplanted hepatoma 22 in mice. Drugs were given intravenously on day 3 and 10 after tumor transplantation. Compared in terms of maximal tolerated doses, VL-LDP-AE at 0.25 mg/kg suppressed the tumor growth by 89.5%, LDM at 0.05 mg/kg by 69.9%, and mitomycin at 1 mg/kg by 35%. Having a molecular weight of 25.2 kDa, VL-LDP-AE was much smaller than other reported antibody-based drugs. The results suggested that VL-LDP-AE would be a promising candidate for tumor targeting therapy. And the 2-step approach could serve as a new technology platform for making a series of highly potent engineered antibody-based drugs for a variety of cancers. PMID:17653664

  7. Effect of Co-Administration of 3',5'-Cyclic Diguanylic Acid with Infectious Bursal Disease Virus Vaccine on Serum Antibody Levels in Broilers

    Directory of Open Access Journals (Sweden)

    Francois Malouin

    2011-01-01

    Full Text Available Cyclic diguanylic acid (c-di-GMP is an intra-cellular bacterial signalling molecule previously shown to possess immune-stimulatory activities. However, the effects of this molecule on chicken immune responses have not been investigated. This study evaluated the humoral immune response following oral administration or Intra-Muscular injection (IM of saline, 10 or 100 nmol c-di-GMP in conjunction with the Infectious Bursal Disease Virus (IBDV vaccine S-706 in 96 broiler chickens. The oral vaccine and the test compounds were administrated at age 14 days and the chickens were then monitored until day 35. Blood samples were collected weekly from 8 birds per treatment to determine the antibody titers. Results showed that oral or IM administration of c-di-GMP did not induce any adverse effect in broiler chickens. Significant increases (p<0.05 in the total Immunoglobulin (Ig A concentrations were observed regardless of the treatments as the birds aged. No significant effect was noted for total IgG and IgM concentrations after any of the sampling days immediately following administration of the compounds. However, on day 35, serum of birds orally administered with 10 and 100 nmol of c-di-GMP showed higher serum IgA antibody concentrations when compared to the serum of birds from the saline control (p<0.05 indicating that c-di-GMP stimulated IgA production in serum and confirming the potential of this molecule as a mucosal adjuvant. No significant effect on serum antivirus antibodies (IBDV infectious bronchitis virus, Newcastle disease virus and avian Reovirus was observed for the 10 or 100 nmol c-di-GMP treatments. The results indicate that studies are warranted on the potential beneficial effects of c-di-GMP on broiler immunity.

  8. Effect of total lymphoid irradiation on IgE antibody responses in rheumatoid arthritis and systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Terr, A.I.; Moss, R.B.; Strober, S.

    1987-12-01

    Thirteen patients with rheumatoid arthritis and four patients with systemic lupus erythematosus and nephritis were treated with total lymphoid irradiation because of severe disease refractory to other forms of treatment. Serum samples before and after irradiation were tested for changes in total serum IgE and for changes in specific IgE antibodies to ryegrass pollen, dust mite, cat dander, and Alternaria. There were no statistically significant changes in total or specific IgE from lymphoid irradiation in these patients. The therapy caused a significant decrease in circulating total lymphocyte and Leu-3 (helper/inducer) T-lymphocyte counts. Therefore, reduction in circulating levels of helper/inducer T cells does not appear to influence preexisting levels of IgE antibodies.

  9. PROTECTIVE LEVELS OF VARICELLA-ZOSTER ANTIBODY DID NOT EFFECTIVELY PREVENT CHICKENPOX IN AN X-LINKED AGAMMAGLOBULINEMIA PATIENT

    Directory of Open Access Journals (Sweden)

    Fernanda Aimée NOBRE

    2015-10-01

    Full Text Available SUMMARY We describe the case of an eight-year-old boy with X-linked agammaglobulinemia who developed mild varicella despite regular intravenous immunoglobulin (IVIG therapy. He maintained protective antibody levels against varicella and the previous batches of IVIG that he received had adequate varicella-specific IgG levels. The case illustrates that IVIG may not prevent VZV infection.

  10. Effectiveness of Intravenous Immunoglobulin Plus Plasmapheresis on Antibody-mediated Rejection or Thrombotic Microangiopathy in Iranian Kidney Transplant Recipient

    OpenAIRE

    Dashti-Khavidaki, Simin; Shojaie, Lida; Hosni, Amin; Khatami, Mohammad Reza; Jafari, Atefeh

    2015-01-01

    Background: Antibody mediated rejection (AMR) and thrombotic microangiopathy (TMA) after kidney transplantation are difficult to differentiate most of the times and both play important roles in kidney allograft loss. Common treatment strategies of these two conditions include plasmapheresis, intravenous immunoglobulin (IVIG) and rituximab. Objectives: This study was designed to assess the efficacy of routine treatment of AMR/TMA in Iranian kidney transplant recipients, which comprises of plas...

  11. Measurement of thyrotropin receptor antibodies (TRAK) with a second generation assay in patients with Graves' disease

    International Nuclear Information System (INIS)

    Aim: The detection of TSH-receptor-antibodies (TRAb) in patients (pts) with Graves' disease (GD) is routinely used in nuclear medicine laboratories. It is performed by commercial, porcine radioreceptorassays (RRA) measuring TSH binding inhibitory activity. A second generation assay using the human, recombinant TSH-receptor was developed during the last years. The manufacturer composed this new assay as a coated tube RRA (CT RRA) and claimed a higher sensitivity for GD. Methods: TRAb was measured in 207 pts with various thyroid disorders and 205 healthy controls using the new coated tube RRA (Fa. B.R.A.H.M.S. Diagnostica GmbH, Berlin, Germany) as well as a conventional RRA (Fa. Medipan Diagnostica GmbH, Selchow, Germany): 60 pts suffering from GD showing a relapse after anti-thyroid drug treatment and before radioiodine therapy, 109 pts with disseminated autonomia (DA) and 38 pts suffering from Hashimoto's thyroiditis. A ROC-analysis was performed to find the optimal decision threshold level for positivity. Results: We found 42/60 TRAb-positive pts with GD in the established RRA (threshold 6 U/L) and 52/60 in the CT RRA, respectively. The sensitivity increased from 70% (RRA) to 86,7% (CT RRA). The CT RRA found 2 false positives (one Hashimoto's and one healthy control) and the RRA detected 3 Hashimoto's and 2 healthy controls as false positive. Conclusion: The increased sensitivity of CT RRA for GD provides an advantage compared to conventional RRA, especially in GD-patients relapsing afte antithyroid drug treatment. Functional sensitivity and Interassayvariation of CT RRA are very precisely compared to conventional RRA. Handling of the new assay is also improved. (orig.)

  12. Antibody-mediated immune suppression is improved when blends of anti-RBC monoclonal antibodies are used in mice.

    Science.gov (United States)

    Bernardo, Lidice; Amash, Alaa; Marjoram, Danielle; Lazarus, Alan H

    2016-08-25

    Although the prevention of hemolytic disease of the fetus and newborn is highly effective using polyclonal anti-D, a recombinant alternative is long overdue. Unfortunately, anti-D monoclonal antibodies have been, at best, disappointing. To determine the primary attribute defining an optimal antibody, we assessed suppression of murine red blood cell (RBC) immunization by single-monoclonal antibodies vs defined blends of subtype-matched antibodies. Allogeneic RBCs expressing the HOD antigen (hen egg lysozyme [HEL]-ovalbumin-human transmembrane Duffy(b)) were transfused into naïve mice alone or together with selected combinations of HEL-specific antibodies, and the resulting suppressive effect was assessed by evaluating the antibody response. Polyclonal HEL antibodies dramatically inhibited the antibody response to the HOD antigen, whereas single-monoclonal HEL antibodies were less effective despite the use of saturating doses. A blend of monoclonal HEL-specific antibodies reactive with different HEL epitopes significantly increased the suppressive effect, whereas a blend of monoclonal antibodies that block each other's binding to the HEL protein did not increase suppression. In conclusion, these data show that polyclonal antibodies are superior to monoclonal antibodies at suppressing the immune response to the HOD cells, a feature that can be completely recapitulated using monoclonal antibodies to different epitopes. PMID:27330002

  13. Antiphospholipid Antibody Syndrome

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Antiphospholipid Antibody Syndrome? Antiphospholipid (AN-te-fos-fo-LIP-id) antibody ... weeks or months. This condition is called catastrophic antiphospholipid syndrome (CAPS). People who have APS also are at ...

  14. [Inhibition of adenovirus reproduction in cell culture by specific antibodies].

    Science.gov (United States)

    Povnytsia, O Iu; Nosach, L M; Zhovnovata, V L; Zahorodnia, S D; Vantsak, N P; Tokarchuk, L V; Polishchuk, O M; Diachenko, N S

    2009-01-01

    The capacity of specific antibodies to inhibit the reproduction of homo- and heterologous adenoviruses in Hela cell added to culture medium after virus adsorption was studied. The inhibiting effect of polyclonal antivirus and monospecific antihexone antibodies to homo- and heterologous adenoviruses was shown. The effect was more expressed when using antibodies to homologous antibodies. The intensity of inhibition depended on antibodies concentration in the medium and infecting dose of the virus. Essential reduction of the quantity of infected cells and a decrease of the titer of adenovirus synthesized in the presence of homo- and heterologous antibodies was shown but adenovirus reproduction was not inhibited completely. PMID:19663330

  15. Production and characterization of peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar

    2012-01-01

    Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies are...... powerful tools in experimental biology and are easily produced to any peptide of choice. A widely used approach for production of peptide antibodies is to immunize animals with a synthetic peptide coupled to a carrier protein. Very important is the selection of the synthetic peptide, where factors such as......, including solid-phase peptide-carrier conjugation and peptide-carrier conjugation in solution. Upon immunization, adjuvants such as Al(OH)(3) are added together with the immunogenic peptide-carrier conjugate, which usually leads to high-titred antisera. Following immunization and peptide antibody...

  16. Functional meaning of scintigraphic and echographic patterns, and of circulating anti-peroxidase antibodies in asymptomatic chronic thyroiditis

    Energy Technology Data Exchange (ETDEWEB)

    Rubello, D.; Gasparoni, P. [Hospital of Castelfranco Veneto, Treviso, (Italy). Endocrinology Service; Rota, G.; Borsato, N.; Zanco, P.; Chierichetti, F.; Ferlin, G. [Hospital of Castelfranco Veneto, Treviso, (Italy). Nuclear Medicine Service

    1996-12-01

    Asymptomatic chronic thyroiditis (ACT) is a variant of the autoimmune thyroiditis characterized by the presence of circulating anti-thyroid antibodies and the absence of palpable goiter. Thyroid function can be normal but a considerable percentage of ACT patients tend to develop subclinical hypothyroidism over time and thus periodical controls of thyroid hormones and TSH levels are needed. At present, useful parameters for predicting the functional out-came of ACT patients are lacking. To investigate this aspect, the authors evaluated 57 consecutive ACT patients (51 females, 6 males, aged 22-56 years) by means of thyroid {sup 99m}Tc-pertechnetate scintigraphy and echography, and by measuring the serum level of anti-peroxidase antibodies (TPOAbs), FT4, T3 and TSH. At first observation, 30 patients were euthyroid whereas 27 had subclinical hypothyroidism. No patient had been previously treated with thyroid hormones. Thyroid scan showed a normal pattern or a diffuse and mild irregular uptake, without differences between euthyroid and subclinical hypothyroid patients. TPOAb levels tend to be higher in patients with subclinical hypothyroidism in comparison to the euthyroid patients (5893{+-}1423 and 3943{+-}912 UI/mL, respectively) but the difference was not statistically significant by using Student`s {sup t-}test. Echography showed a normal pattern in 14 patients, while a diffuse hypoechoic pattern in the other cases, mild in 12, moderate in 19 and marked in 12, as found. A significantly higher prevalence of subclinical hypothyroidism was observed in the group of patients with a moderate or marked hypoechoic pattern in comparison to the group with a normo-echoic or mild hypoechoic pattern (70.4% versus 23.0%, Fisher`s exact test p=0.00003). Furthermore, the 3 patients who developed thyroid failure during a one-year follow-up also presented a moderate or marked hypoechoic pattern. (Abstract Truncated)

  17. The antibody mining toolbox

    OpenAIRE

    D'Angelo, Sara; Glanville, Jacob; Ferrara, Fortunato; Naranjo, Leslie; Gleasner, Cheryl D.; Shen, Xiaohong; Bradbury, Andrew RM; Kiss, Csaba

    2013-01-01

    In vitro selection has been an essential tool in the development of recombinant antibodies against various antigen targets. Deep sequencing has recently been gaining ground as an alternative and valuable method to analyze such antibody selections. The analysis provides a novel and extremely detailed view of selected antibody populations, and allows the identification of specific antibodies using only sequencing data, potentially eliminating the need for expensive and laborious low-throughput ...

  18. Mouse monoclonal antibodies against estrogen receptor.

    Science.gov (United States)

    De Rosa, Caterina; Rossi, Valentina; Abbondanza, Ciro

    2014-01-01

    The production of monoclonal antibodies, by cloning hybridoma derived from the fusion of myeloma cells and spleen lymphocytes, has allowed to obtain great advances in many fields of biological knowledge. The use of specific antibodies to the estrogen receptor, in fact, has been an invaluable method to bring out its mechanisms of action and its effects, both genomic and extra-genomic. Here we describe, step by step, the production of monoclonal antibodies, starting from protocol for antigen preparation to the selection of antibody-secreting hybridoma. PMID:25182770

  19. Antibodies and antisense oligodeoxynucleotides to μ-opioid receptors, selectively block the effects of μ-opioid agonists on intestinal transit and permeability in mice

    OpenAIRE

    Pol, Olga; Valle, Lluís; Sánchez-Blázquez, Pilar; Garzón, Javier; Puig, Margarita M.

    1999-01-01

    We have studied the effects of μ and δ opioids on intestinal function (permeability, PER; gastrointestinal transit, GIT), and their antagonism after the intracerebroventricular (i.c.v.) administration of specific antibodies (ABs) or antisense oligodeoxynucleotides (ODN) to μ-receptors (OR). Central versus peripheral site/s of action of subcutaneous (s.c.) μ-opioids, were also assessed.Male Swiss CD-1 mice were used. GIT was measured with charcoal and PER by the passage of 51Cr-EDTA from blood...

  20. Effect of hepatitis B vaccination in hepatitis B surface antibody-negative pregnant mothers on the vertical transmission of hepatitis B virus from father to infant

    OpenAIRE

    Cao, Li-hua; LI, YUN-RU; WANG, SHOU-YUN; LIU, ZHI-MIN; SUN, SHAO-CHUN; Xu, Dong-Bo; ZHANG, JI-DONG

    2015-01-01

    The aim of the present study was to investigate the effects of vaccination with the hepatitis B vaccine (HBVac) in HB surface antibody (HBsAb)-negative pregnant mothers on the vertical transmission of HB virus (HBV) from father to infant. All the fathers tested positive for the serum HBV DNA and HB surface antigen (HBsAg) markers. The pregnant females were divided into an observation group or a control group depending on whether their serum was HBsAb-negative or positive. A total of 93 health...

  1. Heavy chain only antibodies

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Rahbarizadeh, Fatemeh; Ahmadvand, Davoud;

    2013-01-01

    Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen...

  2. Hepatitis A virus antibody

    International Nuclear Information System (INIS)

    A description is presented of a radioimmunoassay designed to prove the presence of the antibody against the hepatitis A virus (HA Ab, anti-Ha) using an Abbott HAVAB set. This proof as well as the proof of the antibody against the nucleus of the hepatitis B virus is based on competition between a normal antibody against hepatitis A virus and a 125I-labelled antibody for the binding sites of a specific antigen spread all over the surface of a tiny ball; this is then indirect proof of the antibody under investigation. The method is described of reading the results from the number of impulses per 60 seconds: the higher the titre of the antibody against the hepatitis A virus in the serum examined, the lower the activity of the specimen concerned. The rate is reported of incidence of the antibody against the hepatitis A virus in a total of 68 convalescents after hepatitis A; the antibody was found in 94.1%. The immunoglobulin made from the convalescents' plasma showed the presence of antibodies in dilutions as high as 1:250 000 while the comparable ratio for normal immunoglobulin Norga was only 1:2500. Differences are discussed in the time incidence of the antibodies against the hepatitis A virus, the antibodies against the surface antigen of hepatitis B, and the antibody against the nucleus of the hepatitis V virus. (author)

  3. Antibody-Directed Phototherapy (ADP

    Directory of Open Access Journals (Sweden)

    M. Adil Butt

    2013-04-01

    Full Text Available Photodynamic therapy (PDT is a clinically-approved but rather under-exploited treatment modality for cancer and pre-cancerous superficial lesions. It utilises a cold laser or LED to activate a photochemical reaction between a light activated drug (photosensitiser-drug and oxygen to generate cytotoxic oxygen species. These free radical species damage cellular components leading to cell death. Despite its benefits, the complexity, limited potency and side effects of PDT have led to poor general usage. However, the research area is very active with an increasing understanding of PDT-related cell biology, photophysics and significant progress in molecular targeting of disease. Monoclonal antibody therapy is maturing and the next wave of antibody therapies includes antibody-drug conjugates (ADCs, which promise to be more potent and curable. These developments could lift antibody-directed phototherapy (ADP to success. ADP promises to increase specificity and potency and improve drug pharmacokinetics, thus delivering better PDT drugs whilst retaining its other benefits. Whole antibody conjugates with first generation ADP-drugs displayed problems with aggregation, poor pharmacokinetics and loss of immuno-reactivity. However, these early ADP-drugs still showed improved selectivity and potency. Improved PS-drug chemistry and a variety of conjugation strategies have led to improved ADP-drugs with retained antibody and PS-drug function. More recently, recombinant antibody fragments have been used to deliver ADP-drugs with superior drug loading, more favourable pharmacokinetics, enhanced potency and target cell selectivity. These improvements offer a promise of better quality PDT drugs.

  4. Lack of in Vivo Antibody Dependent Cellular Cytotoxicity with Antibody Containing Gold Nanoparticles

    OpenAIRE

    Ahmed, Marya; Pan, Dorothy W.; Davis, Mark E.

    2015-01-01

    Antibody-dependent cellular cytotoxicity (ADCC) is a cytolytic mechanism that can elicit in vivo antitumor effects and can play a significant role in the efficacy of antibody treatments for cancer. Here, we prepared cetuximab, panitumumab, and rituximab containing gold nanoparticles and investigated their ability to produce an ADCC effect in vivo. Cetuximab treatment of EGFR-expressing H1975 tumor xenografts showed significant tumor regression due to the ADCC activity of the antibody in vivo,...

  5. Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection

    OpenAIRE

    Dowall, Stuart David; Callan, Jo; Zeltina, Antra; Al-Abdulla, Ibrahim; Strecker, Thomas; Sarah K Fehling; Krähling, Verena; Bosworth, Andrew; Rayner, Emma; Taylor, Irene; Charlton, Sue; Landon, John; Cameron, Ian; Hewson, Roger; Nasidi, Abdulsalami

    2015-01-01

    The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOT...

  6. Imaging cancer using PET - the effect of the bifunctional chelator on the biodistribution of a 64Cu-labeled antibody

    International Nuclear Information System (INIS)

    Introduction: Use of copper radioisotopes in antibody radiolabeling is challenged by reported loss of the radionuclide from the bifunctional chelator used to label the protein. The objective of this study was to investigate the relationship between the thermodynamic stability of the 64Cu-complexes of five commonly used bifunctional chelators (BFCs) and the biodistribution of an antibody labeled with 64Cu using these chelators in tumor-bearing mice. Methods: The chelators [S-2-(aminobenzyl)1,4,7-triazacyclononane-1,4,7-triacetic acid (p-NH2-Bn-NOTA): 6-[p-(bromoacetamido)benzyl]-1, 4, 8, 11-tetraazacyclotetradecane-N, N', N'', N'''-tetraacetic acid (BAT-6): S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododocane tetraacetic acid (p-NH2-Bn-DOTA): 1,4,7,10-tetraazacyclododocane-N, N', N', N''-tetraacetic acid (DOTA): and 1-N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1, 8-diamine (SarAr)] were conjugated to the anti-GD2 antibody ch14.18, and the modified antibody was labeled with 64Cu and injected into mice bearing subcutaneous human melanoma tumors (M21) (n = 3-5 for each study). Biodistribution data were obtained from positron emission tomography images acquired at 1, 24 and 48 hours post-injection, and at 48 hours post-injection a full ex vivo biodistribution study was carried out. Results: The biodistribution, including tumor targeting, was similar for all the radioimmunoconjugates. At 48 h post-injection, the only statistically significant differences in radionuclide uptake (p 64Cu]ch14.18-p-NH2-Bn-NOTA was 4.74 ± 0.77 per cent of the injected dose per gram of tissue (%ID/g), and for [64Cu]ch14.18-SarAr was 8.06 ± 0.77 %ID/g. Differences in tumor targeting correlated with variations in tumor size rather than which BFC was used. Conclusions: The results of this study indicate that differences in the thermodynamic stability of these chelator-Cu(II) complexes were not associated with significant differences in uptake of the tracer by the tumor

  7. Itolizumab – a humanized anti-CD6 monoclonal antibody with a better side effects profile for the treatment of psoriasis

    Directory of Open Access Journals (Sweden)

    Menon R

    2015-04-01

    Full Text Available Roshni Menon, Brinda G David Department of Dermatology, Venereology and Leprosy, Sri Venkateshwaraa Medical College Hospital and Research Centre, Ariyur, Pondicherry, India Abstract: Management of psoriasis is a challenge to the treating physician. The chronic inflammatory state of psoriasis with exacerbations and remissions necessitate “on-and-off” treatment schedules. The safety profiles of drugs and tolerability issues for patients are important factors to be considered during treatment. Various biological agents targeting T-cells and the inflammatory cytokines are available for systemic treatment of psoriasis. However, major causes of concern while using these drugs are risk of susceptibility to infection and development of anti-drug antibodies, which will affect the pharmacokinetic properties, efficacy, and safety profile of the drug. Itolizumab, a humanized anti-CD6 monoclonal antibody, is a new molecule that acts by immunomodulating the CD6 molecule. CD6 is a co-stimulatory molecule required for optimal T-cell stimulation by the antigen-presenting cells. This step is crucial in T-cell proliferation to form Th1 and Th17 cells, which play a major role in the pathogenesis of psoriasis. This article deals with the properties of Itolizumab and its role in the treatment of psoriasis. Based on the available published data, Itolizumab seems to have a better adverse effects profile and at the same time comparatively less efficacy when compared to other biological agents available for treating psoriasis. Larger studies with longer duration are required to clearly depict the long-term side effects profile. Keywords: Itolizumab, CD6, psoriasis, monoclonal antibody, biologicals 

  8. Effect of an anti-human Co-029/tspan8/Tspan8 mouse monoclonal antibody on tumour growth in a nude mouse model

    Directory of Open Access Journals (Sweden)

    ClaudeBoucheix

    2014-09-01

    Full Text Available New therapeutic agents are needed in digestive tract tumours. Co-029/tspan8 is a tetraspanin frequently expressed on human colorectal tumours, In this work, we report the effects of the monoclonal antibody Ts29.2, targeting Co-029/tspan8, on colorectal tumor cells in vitro and after implantation in nude mice. HT29, Isreco1 and SW480 colorectal tumor cell lines were used for this study. HT29 has a strong endogenous expression of Co-029/tspan8, whereas Isreco1 cells don’t express Co-029/tspan8 and SW480 has only a weak expression. Isreco1 and SW480 were transduced to express Co-029/tspan8 at the same level as HT29. In order to check the specificity of the effect of monoclonal antibody Ts29.2, low Co029/tspan8 expressing SW480 cells were injected simultaneously with transduced cells in the back, on the left and right sides of the mice. With an early treatment, Ts29.2 mAb inhibited growth of tumors expressing Co-029/tspan8 up to 70%, whereas a delayed treatment was less efficient. No effect of the antibody on cell proliferation or apoptosis induction was detected in vitro. No increase of activated caspase 3 labeling was observed in vivo and areas occupied by vessels were not significantly different between treated mice and controls. This suggests that the action of Ts29.2 is linked neither to cellular toxicity nor to the inhibition of the previously reported angiogenic properties of Co-029/tspan8. An inhibition of cell proliferation in vivo is demonstrated by a reduction of the mitotic index in HT29 tumors of Ts29.2 treated mice. The discrepancy between in vitro and in vivo data on cell proliferation suggests that the binding of Ts29.2 to tumour cells may modify their response to signals issued from the microenvironment. Given the restricted pattern of tissue expression of the tetraspanin Co-029/tspan8, these preliminary results put forth for consideration the antibody targeting of this tetraspanin in further investigations for therapeutic

  9. T-cell activation. VI. Inhibitory and stimulatory effects of anti-major histocompatibility complex class I antibodies in allogeneic mixed lymphocyte culture

    DEFF Research Database (Denmark)

    Röpke, M; Röpke, C; Claesson, Mogens Helweg

    1993-01-01

    Murine T splenocytes stimulated in primary allogeneic mixed lymphocyte culture (MLC) were incubated with soluble anti-major histocompatibility complex (MHC) class I monoclonal antibodies. These antibodies induced inhibition in the cytotoxicity of the responding population and this inhibition was...

  10. The effect of hyperimmunization with Neisseria gonorrhoeae on the presence of gonococcal antibody in serum, tissues, and secretions of the rabbit.

    Science.gov (United States)

    Ashton, F E; Collins, F; Wallace, R; Ryan, A; Diena, B B; Lavergne, G

    1977-03-01

    Antibody responses in sera, tissues, and secretions of the urogenital tract and lower respiratory tract of rabbits hyperimmunized with Neisseria gonorrhoeae were examined. Antibody was detected by passive hemagglutination, whole-cell agglutination, bentonite flocculation, and in some cases immunodiffusion-in-gel. Immunization of rabbits either intravenously or intramuscularly resulted in the presence of gonococcal antibodies in the sera, spleens, and tissue of the urogenital tract (vagina, cervix, uterus, and fallopian tubes). Gonococcal antibody was also found in secretions bathing the mucosa of the urogenital tract and lower respiratory tract. Antibodies were not detected in sera, tissues, and secretions of non-immunized rabbits. The spleen was shown to synthesize gonococcal antibody in vitro in response to hyperimmunization. Tissues of the urogenital tract did not appear to synthesize gonococcal antibody thus suggesting and antibodies present in secretions of the urogenital tract were derived mainly from serum. PMID:404007

  11. Monoclonal antibodies and cancer

    International Nuclear Information System (INIS)

    The usefulness of radiolabeled monoclonal antibodies for imaging and treatment of human (ovarian) cancer was investigated. A review of tumor imaging with monoclonal antibodies is presented. Special attention is given to factors that influence the localization of the antibodies in tumors, isotope choice and methods of radiolabeling of the monoclonal antibodies. Two monoclonal antibodies, OC125 and OV-TL3, with high specificity for human epithelial ovarian cancer are characterized. A simple radio-iodination technique was developed for clinical application of the monoclonal antibodies. The behavior of monoclonal antibodies in human tumor xenograft systems and in man are described. Imaging of tumors is complicated because of high background levels of radioactivity in other sites than the tumor, especially in the bloodpool. A technique was developed to improve imaging of human tumor xenographs in nude mice, using subtraction of a specific and a non-specific antibody, radiolabeled with 111In, 67Ga and 131I. To investigate the capability of the two monoclonal antibodies, to specifically localize in human ovarian carcinomas, distribution studies in mice bearing human ovarian carcinoma xenografts were performed. One of the antibodies, OC125, was used for distribution studies in ovarian cancer patients. OC125 was used because of availability and approval to use this antibody in patients. The same antibody was used to investigate the usefulness of radioimmunoimaging in ovarian cancer patients. The interaction of injected radiolabeled antibody OC125 with circulating antigen and an assay to measure the antibody response in ovarian cancer patients after injection of the antibody is described. 265 refs.; 30 figs.; 19 tabs

  12. Bioconjugation of antibodies to horseradish peroxidase (hrp)

    Science.gov (United States)

    The bioconjugation of an antibody to an enzymatic reporter such as horseradish peroxidase (HRP) affords an effective mechanism by which immunoassay detection of a target antigen can be achieved. The use of heterobifunctional cross—linkers to covalently link antibodies to HRP provides a simple and c...

  13. Thyrotropin receptor antibodies and its clinical application

    International Nuclear Information System (INIS)

    Thyrotropin receptor antibodies (TRAb) are not homogeneous, which are composed by four antibodies at least. TRAb plays very important roles in autoimmune thyroid diseases ad off-thyroid symptoms associated, and other thyroiditis in clinical diagnosis, assessment of curative effects, determination of the time to stop medicine, prognostication of recurrence and inspection of high risk population

  14. The Effects of Somatic Hypermutation on Neutralization and Binding in the PGT121 Family of Broadly Neutralizing HIV Antibodies

    Science.gov (United States)

    Vigneault, Francois; Julien, Jean-Philippe; Briney, Bryan; Ramos, Alejandra; Saye, Karen F.; Le, Khoa; Mahan, Alison; Wang, Shenshen; Kardar, Mehran; Yaari, Gur; Walker, Laura M.; Simen, Birgitte B.; St. John, Elizabeth P.; Chan-Hui, Po-Ying; Swiderek, Kristine; Kleinstein, Stephen H.; Alter, Galit; Seaman, Michael S.; Chakraborty, Arup K.; Koller, Daphne; Wilson, Ian A.; Church, George M.; Burton, Dennis R.; Poignard, Pascal

    2013-01-01

    Broadly neutralizing HIV antibodies (bnAbs) are typically highly somatically mutated, raising doubts as to whether they can be elicited by vaccination. We used 454 sequencing and designed a novel phylogenetic method to model lineage evolution of the bnAbs PGT121–134 and found a positive correlation between the level of somatic hypermutation (SHM) and the development of neutralization breadth and potency. Strikingly, putative intermediates were characterized that show approximately half the mutation level of PGT121–134 but were still capable of neutralizing roughly 40–80% of PGT121–134 sensitive viruses in a 74-virus panel at median titers between 15- and 3-fold higher than PGT121–134. Such antibodies with lower levels of SHM may be more amenable to elicitation through vaccination while still providing noteworthy coverage. Binding characterization indicated a preference of inferred intermediates for native Env binding over monomeric gp120, suggesting that the PGT121–134 lineage may have been selected for binding to native Env at some point during maturation. Analysis of glycan-dependent neutralization for inferred intermediates identified additional adjacent glycans that comprise the epitope and suggests changes in glycan dependency or recognition over the course of affinity maturation for this lineage. Finally, patterns of neutralization of inferred bnAb intermediates suggest hypotheses as to how SHM may lead to potent and broad HIV neutralization and provide important clues for immunogen design. PMID:24278016

  15. Randomized trial: The effect of oral polio vaccine at birth on polio antibody titers at 6 weeks and 6 months of age

    Directory of Open Access Journals (Sweden)

    Anna Sofie Hansen

    2014-01-01

    Conclusions: OPV0 may contribute to early polio protection, particularly in children of mothers with low antibody levels. However, OPV0 did not contribute to overall polio immunity after subsequent doses of OPV were given, and was associated with significantly lower antibody titers in children of mothers with high antibody levels. However, it did not negatively affect the proportion of seropositive children.

  16. Radioimmunotherapy with engineered antibody fragments

    International Nuclear Information System (INIS)

    Authors have developed and begun evaluating radiometal-chelated (213Bi) engineered antibody fragments as radioimmunotherapy agents that target the HER2/neu (c-erbB-2) antigen. The diabody format was found to have 40-fold greater affinity for HER2/neu and to be associated with significantly greater tumor localization than is achieved with scFv molecule. It is shown that short-lived isotopes like 213Bi would be most effective when used in conjunction with antibodies that targeted diffuse malignancies (leukemia or lymphoma) or when used for very rapid pretargeted radioimmunotherapy application in which the radioisotope is conjugated to a very small ligand

  17. The effect of Aquablend Avian probiotic ® including Lactobacillus, Streptococcus and Bifidobacterium on systemic antibody response against Newcastle and Influenza disease vaccine in broiler chickens

    Directory of Open Access Journals (Sweden)

    Talazadeh

    2016-05-01

    Full Text Available Background Finding alternatives to antibiotics for poultry production is very important because there are increasing concerns about antibiotic resistance. So, researchers have been directed to the research back to natural antimicrobial products. Some researchers stated that probiotics can stimulate the immune system and play an important role in shaping the immune system. Objectives The aim of this study was to examine the effect of a commercial probiotic mixture (Aquablend Avian® supplementation to the drinking water of broiler chickens on the immune response against Newcastle and influenza diseases vaccines. Materials and Methods In this study, 180 one-day-old broiler chickens were purchased and divided randomly into 3 groups (n = 60 for each group. Chickens in groups A and B received 300 mg of the probiotic in drinking water for first 3 days and first 7 days, respectively. Chickens in group C were kept as a control group and did not receive probiotic. All groups were vaccinated with live Newcastle vaccine (B1 strain intraocularly on 8th day, and AI-ND killed vaccine (subtype H9N2 subcutaneously at the back of the neck on 8th day. Two mL of blood samples were collected before vaccination as well as on days 14, 28 and 35 postimmunization. Ten chickens of each group were bled randomly and an antibody titer against Newcastle disease vaccine and AI-ND killed vaccine (subtype H9N2 was determined by the hemagglutination-inhibition test. Results The results of the present study showed that oral administration of the probiotic for 7 days significantly increased the specific antibody response to Newcastle vaccine compared to the control group (0.75 - 1.6 log, based on log2, while the probiotic administration had no significant effect on antibody productions against avian influenza vaccine as compared to the control group. Conclusions Oral administration of Aquablend Avian® probiotic strains including Lactobacillus, Streptococcus and Bifidobacterium

  18. Subclinical Hypothyroidism and the Effect of Autoimmunity on the Echocardiography Indices of Left Ventricular Function, Lipid Profile, and Inflammatory Markers

    Directory of Open Access Journals (Sweden)

    Zohreh Moossavi

    2015-03-01

    Full Text Available Background: Subclinical hypothyroidism (Sch is the most frequent thyroid disease. The relationship between overt hypothyroidism and cardiovascular diseases has been well documented, but conflicting data have remained regarding Sch. Objectives: The present study aimed to assess the effect of Sch on increasing the risk of cardiovascular involvement considering the autoimmune subset. Patients and Methods: This case-control study was conducted on thirty patients with Sch and 30 healthy controls. Serum levels of thyroperoxidase antibody (TPOab, lipids, hsCRP, homocysteine, and ferritin were measured. Besides, conventional echocardiographic study and tissue Doppler imaging (including strain rate indices was done to evaluate Left Ventricular (LV systolic function. Results: The results showed a significant difference between the Sch patients and the controls regarding the serum level of triglyceride (117.43 ± 63.51 mg/dL vs. 86.86 ± 41.57, P = 0.031, echocardiographic parameters (longitudinal systolic strain rate [SRs: -1.006 ± 0.4 vs. -1.26 ± 0.16, P = 0.002; SRl: -1.43 ± 0.27 vs. -1.68 ± 0.29, P = 0.001], and Sm of septal mitral annulus (6.90 ± 0.6 vs. 7.43 ± 0.8, P = 0.006]. However, no significant difference was observed between the two groups regarding the serum levels of the inflammatory markers. Moreover, a significant correlation was found between TSH and Sm (r = -0.36, P = 0.005 and longitudinal systolic strain rate (SRs: r = 0.42, P < 0.001; SRl: r = 0.40, P = 0.001. Systolic strain rate was significantly lower in the TPOab positive patients (-0.99 ± 0.18 vs. -1.15 ± 0.25, P = 0.047. Conclusions: The clear association between Sch and subclinical LV systolic dysfunction which was more evident in the subgroup of patients with circulating anti-thyroid antibodies would remind a greater emphasis for considering the subgroup of TPOab positive patients for directing toward hormone replacement.

  19. Bovine Colostral Antibody Against Verotoxin 2 Derived from Escherichia coli O157:H7: Resistance to Proteases and Effects in Beagle Dogs

    OpenAIRE

    Kuribayashi, Takashi; Seita, Tetsuro; Matsumoto, Mariko; Furuhata, Katsunori; Tagata, Kazutoshi; Yamamoto, Shizuo

    2009-01-01

    A bovine colostral antibody against verotoxin (VT) 2 of Escherichia coli O157:H7 was administered orally to beagle dogs. The antibody remained in the dogs’ small intestine for at least 2 h, whereas little serum antibody remained 1.5 h after administration. Furthermore, the antibody activity of secretory IgA did not change until 2 h after administration; however, the activity of IgG and IgM antibodies decreased by approximately 60% and 40% at 2 h after administration, respectively. Seven beagl...

  20. Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection

    Science.gov (United States)

    Dowall, Stuart David; Callan, Jo; Zeltina, Antra; Al-Abdulla, Ibrahim; Strecker, Thomas; Fehling, Sarah K.; Krähling, Verena; Bosworth, Andrew; Rayner, Emma; Taylor, Irene; Charlton, Sue; Landon, John; Cameron, Ian; Hewson, Roger; Nasidi, Abdulsalami; Bowden, Thomas A.; Carroll, Miles W.

    2016-01-01

    The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOTAb, was prepared from the antisera and used for an in vivo guinea pig study. When EBOTAb was delivered 6 hours after challenge, all animals survived without experiencing fever or other clinical manifestations. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease. PMID:26715676

  1. Development of a Cost-effective Ovine Polyclonal Antibody-Based Product, EBOTAb, to Treat Ebola Virus Infection.

    Science.gov (United States)

    Dowall, Stuart David; Callan, Jo; Zeltina, Antra; Al-Abdulla, Ibrahim; Strecker, Thomas; Fehling, Sarah K; Krähling, Verena; Bosworth, Andrew; Rayner, Emma; Taylor, Irene; Charlton, Sue; Landon, John; Cameron, Ian; Hewson, Roger; Nasidi, Abdulsalami; Bowden, Thomas A; Carroll, Miles W

    2016-04-01

    The highly glycosylated glycoprotein spike of Ebola virus (EBOV-GP1,2) is the primary target of the humoral host response. Recombinant EBOV-GP ectodomain (EBOV-GP1,2ecto) expressed in mammalian cells was used to immunize sheep and elicited a robust immune response and produced high titers of high avidity polyclonal antibodies. Investigation of the neutralizing activity of the ovine antisera in vitro revealed that it neutralized EBOV. A pool of intact ovine immunoglobulin G, herein termed EBOTAb, was prepared from the antisera and used for an in vivo guinea pig study. When EBOTAb was delivered 6 hours after challenge, all animals survived without experiencing fever or other clinical manifestations. In a second series of guinea pig studies, the administration of EBOTAb dosing was delayed for 48 or 72 hours after challenge, resulting in 100% and 75% survival, respectively. These studies illustrate the usefulness of EBOTAb in protecting against EBOV-induced disease. PMID:26715676

  2. The effect of internalizing human single chain antibody fragment on liposome targeting to epithelioid and sarcomatoid mesothelioma

    Science.gov (United States)

    Iyer, Arun K.; Su, Yang; Feng, Jinjin; Lan, Xiaoli; Zhu, Xiaodong; Liu, Yue; Gao, Dongwei; Seo, Youngho; VanBrocklin, Henry F.; Broaddus, V. Courtney; Liu, Bin; He, Jiang

    2011-01-01

    Immunoliposomes (ILs) anchored with internalizing human antibodies capable of targeting all subtypes of mesothelioma can be useful for targeted imaging and therapy of this malignant disease. The objectives of this study were to evaluate both the in vitro and in vivo tumor targeted internalization of novel internalizing human single chain antibody (scFv) anchored ILs on both epithelioid (M28) and sarcomatoid (VAMT-1) subtypes of human mesothelioma. ILs were prepared by post-insertion of mesothelioma-targeting human scFv (M1) onto preformed liposomes and radiolabeled with 111In (111In-IL-M1), along with control non-targeted liposomes (111In-CL). Incubation of 111In-IL-M1 with M28, VAMT-1, and a control non-tumorigenic cell-line (BPH-1) at 37°C for 24 h revealed efficient binding and rapid internalization of ILs into both subtypes of tumor cells but not into the BPH-1 cells; internalization accounted for approximately 81-94% of total cell accumulation in mesothelioma cells compared to 37-55% in control cells. In tumor bearing mice intravenous (i.v.) injection of 111In-IL-M1 led to remarkable tumor accumulation: 4 % and 4.7% injected dose per gram (% ID/g) for M28 and VAMT-1 tumors, respectively, 48 h after injection. Furthermore, tumor uptake of 111In-IL-M1 in live xenograft animal models was verified by single photon emission computed tomography (SPECT/CT). In contrast, i.v. injection of 111In-CL in tumor-bearing mice revealed very low uptake in both subtypes of mesothelioma, 48 h after injection. In conclusion, M1 scFv-anchored ILs showed selective tumor targeting and rapid internalization into both epithelioid and sarcomatoid subtypes of human mesothelioma, demonstrating its potential as a promising vector for enhanced tumor drug targeting. PMID:21255833

  3. Antiphospholipid antibodies and infertility.

    Science.gov (United States)

    Chighizola, C B; de Jesus, G R

    2014-10-01

    Since the late 1980s some publications have proposed that antiphospholipid antibodies (aPL) may have some relationship with infertility, considering reported deleterious effects that aPL exert on trophoblast proliferation and growth. Although not included in current classification criteria for antiphospholipid syndrome, many physicians investigate for aPL in patients with a history of infertility, including antibodies not listed in classification criteria, and most of those patients will receive anticoagulant therapy if any of those antibodies have a result considered positive. A review of literature was conducted searching for studies that investigated the association of aPL and infertility and if aPL positivity alters in vitro fertilization (IVF) outcome. The definition of infertility, routine work-up to exclude other causes of infertility, definition of IVF failure as inclusion criteria and control populations were heterogeneous among studies. Most of them enrolled women over 40 years of age, and exclusion of other confounding factors was also inconsistent. Of 29 studies that assessed aPL positivity rates in infertile women, the majority had small sample sizes, implying a lack of power, and 13 (44.8%) reported higher frequency of aPL in infertile patients compared to controls, but most of them investigated a panel of non-criteria aPL tests, whose clinical significance is highly controversial. Only two studies investigated all three criteria tests, and medium-high titer of anticardiolipin cut-off conforming to international guidelines was used in one study. Considering IVF outcome, there was also disparity in this definition: few studies assessed the live birth rate, others the implantation rate. Of 14 publications that addressed the relationship between aPL and IVF outcome, only two described a detrimental effect of these autoantibodies. In conclusion, available data do not support an association between aPL and infertility, and aPL positivity does not seem to

  4. Engineering antibody therapeutics.

    Science.gov (United States)

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  5. Effect of the antibody of brain-derived neurotrophic factor on the rat with ischemic injury from obstruction of middle cerebral artery%脑源性神经营养因子抗体对大脑中动脉阻塞大鼠缺血损伤的影响

    Institute of Scientific and Technical Information of China (English)

    陈英辉; 王根发; 陈兴华; 姚革; 陈伟; 周永炜

    2003-01-01

    AIM:To observe the effect of the antibody of brain derived neurotrophic factor(BDNF) by cortical microinjection on hippocampal ischemic injury rats.METHODS:Preparation of local cerebral ischemic reperfusion injury model: cortical stereostaxic approach, microinjection of BDNF antibody. Applied immunohistochemical method to observe distribution of BDNF in cortex after injection of the antibody,to observe the alteration of ischemic injury between control group and BDNF antibody group.RESULT: The volume of cerebral infarction in BDNF antibody group was larger than control group.CONCLUSION: BDNF has protection function for cerebral ischemia.

  6. Effect of days in milk and milk yield on testing positive in milk antibody ELISA to Mycobacterium avium subsp. paratuberculosis in dairy cattle

    DEFF Research Database (Denmark)

    Nielsen, Søren Saxmose; Toft, Nils

    2012-01-01

    Milk samples are becoming more used as a diagnostic specimen for assessment of occurrence of antibodies to Mycobacterium avium subsp. paratuberculosis (MAP). This study assessed the effect of days in milk (DIM) and milk yield on testing positive in a commercial MAP specific milk antibody ELISA...... among 222,774 Danish Holstein cows. Results showed that odds of testing positive on 1-2 DIM were 9-27 times higher than the rest of lactation, where the chance of testing positive varied less. The reason is most likely a high concentration of non-specific antibodies in colostrum. Consequently, samples...... from the first couple of DIM should be excluded from MAP testing until further information on their significance is established. Milk yield also had a significant effect on odds of testing positive due to its diluting effect. Inclusion of milk yield in the interpretation of test results could improve...

  7. Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion.

    Science.gov (United States)

    McNeel, Douglas G; Eickhoff, Jens; Lee, Fred T; King, David M; Alberti, Dona; Thomas, James P; Friedl, Andreas; Kolesar, Jill; Marnocha, Rebecca; Volkman, Jennifer; Zhang, Jianliang; Hammershaimb, Luz; Zwiebel, James A; Wilding, George

    2005-11-01

    At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the alpha(v)beta(3) integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the alpha(v)beta(3) integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at alpha(v)beta(3) could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, >1 and >2 years) on

  8. Progranulin antibodies in autoimmune diseases.

    Science.gov (United States)

    Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael

    2013-05-01

    Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. PMID:23149338

  9. Antiphospholipid antibody: laboratory, pathogenesis and clinical manifestations

    Directory of Open Access Journals (Sweden)

    T. Ziglioli

    2011-06-01

    Full Text Available Antiphospholipid antibodies (aPL represent a heterogeneous group of antibodies that recognize various antigenic targets including beta2 glycoprotein I (β2GPI, prothrombin (PT, activated protein C, tissue plasminogen activator, plasmin and annexin A2. The most commonly used tests to detect aPL are: lupus anticoagulant (LAC, a functional coagulation assay, anticardiolipin antibody (aCL and anti-β2GPI antibody (anti-β2GPI, which are enzyme-linked immunoassay (ELISA. Clinically aPL are associated with thrombosis and/or with pregnancy morbidity. Apparently aPL alone are unable to induce thrombotic manifestations, but they increase the risk of vascular events that can occur in the presence of another thrombophilic condition; on the other hand obstetrical manifestations were shown to be associated not only to thrombosis but mainly to a direct antibody effect on the trophoblast.

  10. "Unconventional" Neutralizing Activity of Antibodies Against HIV

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Neutralizing antibodies are recognized to be one of the essential elements of the adaptive immune response that must be induced by an effective vaccine against HIV. However, only a limited number of antibodies have been identified to neutralize a broad range of primary isolates of HIV-1 and attempts to induce such antibodies by immunization were unsuccessful. The difficulties to generate such antibodies are mainly due to intrinsic properties of HIV-1 envelope spikes, such as high sequence diversity, heavy glycosylation, and inducible and transient nature of certain epitopes. In vitro neutralizing antibodies are identified using "conventional" neutralization assay which uses phytohemagglutinin (PHA)-stimulated human PBMCs as target cells. Thus, in essence the assay evaluates HIV-1 replication in CD4+ T cells. Recently, several laboratories including us demonstrated that some monoclonal antibodies and HIV-1-specific polyclonal IgG purified from patient sera, although they do not have neutralizing activity when tested by the "conventional" neutralization assay, do exhibit potent and broad neutralizing activity in "unconventional" ways. The neutralizing activity of these antibodies and IgG fractions is acquired through post-translational modifications, through opsonization of virus particles into macrophages and immature dendritic cells (iDCs), or through expression of antibodies on the surface of HIV-1-susceptible cells. This review will focus on recent findings of this area and point out their potential applications in the development of preventive strategies against HIV.

  11. [Effect of erythrocyte preserved for different lengths of time on anti-D antibody identification with three blood matching tests].

    Science.gov (United States)

    Xiao, Rui-Qing; Lin, Wu-Cun; Xu, Dan; Zeng, Jie; Wu, Jian-Jun; Zhao, Shu-Ming

    2003-10-01

    The specificity of the antigens and length of preservation time of erythrocytes are the interfering factors in blood group serological tests. In order to clarify the influence of preservation time of erythrocytes on the blood matching test, the titers of anti-D antibody were detected with papain method, BioVue cross matching card and DianaGel cross matching card in 7 series of panel red blood cells preserved for various length of time (0 to 9 months). The results showed that the titer of micro-column gel test (DianaGel card) was one tube higher than that of column agglutinating test (BioVue card). The titer of erythrocytes preserved for 9 months was as high as 256 tested by DianaGel card, but it was only 2 by papain method in the same anti-serum. It is suggested that there was no obvious difference between the results of micro-column gel test and column agglutinating test, and titer of papain method was the lowest. PMID:14575550

  12. Effect of a booster-dose of rabies vaccine on the duration of virus neutralizing antibody titers in bovines

    Directory of Open Access Journals (Sweden)

    Albas Avelino

    1998-01-01

    Full Text Available Humoral immune response using inactivated rabies vaccine was studied in 35 nelore cross-bred bovines of western region of São Paulo state. Ninety days after vaccination, 13 (92.8% animals presented titers 30.5IU/ml, through mouse neutralization test. After 180 days, 9 (64.3% sera showed titers 30.5IU/ml, after 270 days, only one (7.1% showed a titer of 0.51IU/ml, and after 360 days, all animals showed titers < 0.5IU/ml. Group of animals receiving booster dose 30 days after vaccination presented, two months after, all with titers > 0.5IU/ml. At 180 days, 17 (80.9% sera presented titers > 0.5IU/ml; at 270 days, 15 (71.4%, with titers 30.5IU/ml and at 360 days, 4 (19.0%, with titers 30.5IU/ml. Booster-dose ensured high levels of neutralizing antibodies for at least three months, and 240 days after revaccination, 71.4% of animals were found with titers 30.5IU/ml.

  13. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  14. Protective effects of chicken egg yolk antibody (IgY) against experimental Vibrio splendidus infection in the sea cucumber (Apostichopus japonicus).

    Science.gov (United States)

    Li, Xiaoyu; Jing, Kailin; Wang, Xitao; Li, Yuan; Zhang, Meixia; Li, Zhen; Xu, Le; Wang, Lili; Xu, Yongping

    2016-01-01

    Vibrio splendidus is one of the most harmful pathogens associated with skin ulceration syndrome in the sea cucumber (Apostichopus japonicus) due to its high virulence and frequency of appearance. The objective of this study was to determine the effectiveness of chicken egg yolk antibody (IgY) against V. splendidus infection in the sea cucumber. Whole V. splendidus cells were used as an immunogen to immunize 20 White Leghorn hens (25 weeks old). IgY was produced from egg yolks obtained from these immunized hens using water dilution, two-step salt precipitation and ultrafiltration. The purity of the IgY produced was approximately 83%. Enzyme-linked Immunosorbent Assay indicated a high specificity for IgY with a maximum antibody titer of 320,000. The growth of V. splendidus in liquid medium was significantly inhibited by IgY in a dose-dependent manner at concentrations ranging from 1 to 10 mg/mL. The protective effects of IgY were evaluated in sea cucumber by intraperitoneally injecting anti-V. splendidus IgY antibodies (10 mg/mL) or immersing the sea cucumber in aqueous IgY (1 g/L) after an intraperitoneal injection of V. splendidus. Intraperitoneal injection resulted in an 80% survival while immersion resulted in a 75% survival during the 11-day experimental period. The survival rates were significantly higher than the positive control and the non-specific IgY group (P < 0.05). As well, the bacterial burden in the respiratory tree, intestine and coelomic liquid was significantly (P < 0.05) lower in sea cucumber treated with specific IgY than those treated with non-specific IgY. The phagocytosis of coelomocytes for V. splendidus in the presence of specific IgY was significantly (P < 0.05) higher than that obtained with non-specific IgY or without IgY, suggesting that specific IgY enhanced phagocytic activity. The current work suggests that specific IgY has potential for protecting sea cucumbers against V. splendidus infection. PMID:26592708

  15. An analysis of tumor cell kinetics, using the Ki-67 monoclonal antibody, and the correlation of these kinetics on the radiotherapeutic effect

    International Nuclear Information System (INIS)

    The correlation between the kinetics of tumor cells, analyzed by immunostaining using the Ki-67 monoclonal antibody, and the effect of these kinetics on radiotherapy has been examined in 23 patients with either head and neck cancer or uterine cancer. In uterine cancer patients who had a higher Ki-67-positive cell fraction (KPF), tumor regression began early and was rapid up to 30 Gy, so that a good radiotherapeutic tumor response was obtained. In head and neck cancer patients with a high KPF, an early tumor regression was also seen, although it did not correlate with radiotherapeutic tumor response. This discrepancy was though to be caused by the 'repopulation' during radiotherapy, and the discrepancy was greater in patients who had a higher KPF and a longer treatment time. (author)

  16. T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo.

    Science.gov (United States)

    English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

    2014-10-01

    Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. PMID:24890382

  17. Inhibitory Effect of Anti-HER-2 Anti-CD3 Bi-specific Antibody on the Growth of Gastric Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    To evaluate the effect of anti-HER-2 × anti-CD3 bi-specific antibody (BsAb) on the growth of HER-2/neu-expressing human gastric carcinoma in vitro and in vivo, an MTT assay was carried out to test the inhibitive rates of herceptin, anti-CD3 and BsAb antibodies on SGC-7901 gastric carcinoma cells. Immunocytochemistry methods were used to test the HER-2 level of SGC-7901. Nude mice models were employed to test the effect of HER-2 CD3 BsAb combined with effector cells( peripheral blood lymphatic cells of healthy human beings) on the growth of tumors in animals. Compared with that of the untreated control group, the tumor cell growth rates in vitro and in vivo will both be significantly inhibited when treated with effector cells combined with anti-CD3 McAb, herceptin or HER2 CD3 BsAb (p <0. 05), and the growth inhibition is the most remarkable in the group treated with HER2 CD3 BsAb combined with effector cells. The growth of tumor xenografts will also be significantly inhibited in the group treated with HER2CD3 BsAb combined with effector cells when compared with that in the group treated with anti-CD3 McAb or the group treated with herceptin combined with effector cells(p < 0. 05). We can conclude that HER-2/neu is possibly a useful target for immunotherapy of gastric carcinoma, and anti-HER2 × anti-CD3 BsAb has evident anti-tumor efficacy both, in vitro and in vivo.

  18. Affinity purification of antibodies

    Science.gov (United States)

    Antibodies are provided in a variety of formats that includes antiserum, hybridoma culture supernatant or ascites. They can all be used successfully in crude form for the detection of target antigens by immunoassay. However, it is advantageous to use purified antibody in defined quantity to facil...

  19. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  20. Production Of Human Antibodies

    Science.gov (United States)

    Sammons, David W.; Neil, Garry A.

    1993-01-01

    Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

  1. RBC Antibody Screen

    Science.gov (United States)

    ... the baby is Rh-positive and the mother's antibody status is negative for anti-D, the mother is given additional RhIG. This test also may be used to help diagnose autoimmune-related hemolytic anemia ... when a person produces antibodies against his or her own RBC antigens. This ...

  2. Characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71 infection.

    Directory of Open Access Journals (Sweden)

    Xiao Fang Lim

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 is the main causative agent of Hand, Foot and Mouth disease (HFMD and is associated with severe neurologic complications and mortalities. At present, there is no vaccine or therapeutic available for treatment. METHODOLOGY/PRINCIPAL FINDING: In this study, we generated two mAbs, denoted as mAb 51 and 53, both targeting the same linear epitope on VP1 capsid protein, spanning amino acids 215-219. In comparison, mAb 51 belonging to isotype IgM possesses neutralizing activity in vitro, whereas, mAb 53 belonging to isotype IgG1 does not have any neutralizing ability, even towards its homologous strain. When mAb 51 at 10 µg/g of body weight was administered to the 2-week-old AG129 mice one day prior to lethal challenge, 100% in vivo passive protection was observed. In contrast, the isotype control group mice, injected with an irrelevant IgM antibody before the challenge, developed limb paralysis as early as day 6 post-infection. Histological examination demonstrated that mAb 51 was able to protect against pathologic changes such as neuropil vacuolation and neuronal loss in the spinal cord, which were typical in unprotected EV-71 infected mice. BLAST analyses of that epitope revealed that it was highly conserved among all EV71 strains, but not coxsachievirus 16 (CA16. CONCLUSION: We have defined a linear epitope within the VP1 protein and demonstrated its neutralizing ability to be isotype dependent. The neutralizing property and highly conserved sequence potentiated the application of mAb 51 and 53 for protection against EV71 infection and diagnosis respectively.

  3. Effects of Gan lian Yu ping feng powder on the antibody titers to infectious laryngotracheitis vaccine and some nonspecific immune indexes in chickens.

    Science.gov (United States)

    Chunmei, Kong; Zhujun, Zhao; Xiuhui, Zhong

    2013-01-01

    The study was conducted in order to investigate the immuno-enhancing property of the Chinese herbal formula, Gan lian Yu ping feng powder. Three hundred and thirty six 45-day-old chicks were randomly divided into eight groups. The chicks in groups A, B, C were orally given 0.25 g/mL (low-), 0.5 g/mL (middle-) and 1.0 g/mL (high) dose of Gan lian Yu ping feng powder in the drinking water respectively for 3 days consecutively. They were then immunised with infectious laryngotracheitis vaccine (ILTV) on the 4th day. Groups D, E, F were given 0.25 g/mL, 0.5 g/mL and 1.0 g/mL dose of Gan lian Yu ping feng powder respectively after the immunisation for three days consecutively. Group G was Wen du qing (a government approved herbal product for ILT) control group, and group H was blank control group. At 52, 59, 73, 87 days of age, 8 chicks of each group were selected randomly for blood sampling to determine the levels of IFN-γ, IL-4 and the antibody of ILT. Then the chickens were sacrificed, with the thymus, spleen and Bursa of Fabricius being weighed for the calculation of immune organ indexes. The results showed that high and middle dosages of Gan lian Yu ping feng powder given at the day before immunisation and 3 days after immunisation elevated not only the contents of IFN-γ, the antibody titers of ILT (P<0.01) and the immune organ indexes (P<0.05) significantly, but also reduced the contents of IL-4. There was a significantly different degree of enhancement in the content of IFN-γ, the antibody of ILT (P<0.01) and the immune organ index (P<0.05). The results indicate that Gan lian Yu ping feng powder effectively improves the immunity in chickens. PMID:24146504

  4. Selection of Recombinant Human Antibodies.

    Science.gov (United States)

    Tomszak, Florian; Weber, Susanne; Zantow, Jonas; Schirrmann, Thomas; Hust, Michael; Frenzel, André

    2016-01-01

    Since the development of therapeutic antibodies the demand of recombinant human antibodies is steadily increasing. Traditionally, therapeutic antibodies were generated by immunization of rat or mice, the generation of hybridoma clones, cloning of the antibody genes and subsequent humanization and engineering of the lead candidates. In the last few years, techniques were developed that use transgenic animals with a human antibody gene repertoire. Here, modern recombinant DNA technologies can be combined with well established immunization and hybridoma technologies to generate already affinity maturated human antibodies. An alternative are in vitro technologies which enabled the generation of fully human antibodies from antibody gene libraries that even exceed the human antibody repertoire. Specific antibodies can be isolated from these libraries in a very short time and therefore reduce the development time of an antibody drug at a very early stage.In this review, we describe different technologies that are currently used for the in vitro and in vivo generation of human antibodies. PMID:27236551

  5. Effects of a superantigen-antibody recombinant fusion protein (r-C242 Fab-SEA) on toxicological responses in the anaesthetised rabbit

    International Nuclear Information System (INIS)

    The objective was to study toxin-induced effects on physiological parameters in the rabbit and whether these parameters show dose-response and co-variation after administration of a recombinant fusion protein between staphylococcal enterotoxin (SE) and the Fab fragment of an antibody. Rabbits are very sensitive to SE toxins and the cardiovascular and immune effects are similar to those observed in septic shock in man. The test compound, r-C242 Fab-SEA, was administered intravenously to anaesthetised New Zealand white rabbits at doses in the range of 0.00005-50 μg/kg. All rabbits were checked for titres of anti-SEA antibodies before entering the experiment, since they could neutralise the effect of the test compound. Heart rate, blood pressure and body temperature were continuously monitored before and during 6 h after dosing. Immediately before the start of administration and 3 and 6 h during the experiment, blood gases (pO2 and pCO2), pH, haematology, clinical chemistry, cytokine response (TNF-α) and trace elements (Mn, Cu, Zn, Se, Ag, Cd, Hg and Pb) were measured. No mortality occurred, but at 50 μg/kg severe adverse clinical signs developed. The decrease in blood pressure was weakly dose-related. Heart rate, ECG, body temperature, pCO2 and pH were not affected by the treatment. pO2 tended to increase as a function of time, but not in relation to dose. WBC and PLT decreased dose dependently. TNF-α was not affected by the treatment. The major effects on clinical chemistry were a dose-dependent increase in AST and creatinine. Potassium and urea showed dose dependent increases, mainly at higher doses, though these changes were of less value for drug selection purposes. Trace element changes were observed, including an increase in Mn and a decrease of Zn at all doses. The Cu/Zn ratio decreased below normal at low doses, whereas at high doses in which adverse effects developed, it increased above normal. Post mortem examination revealed minimal to moderate dose

  6. Significance of the 19-kDa hemolymph protein HP19 for the development of the rice moth Corcyra cephalonica: morphological and biochemical effects caused by antibody application.

    Science.gov (United States)

    Arif, Abul; Gullipalli, Damodar; Scheller, Klaus; Dutta-Gupta, Aparna

    2007-09-01

    The hemolymph protein HP19 of the rice moth, Corcyra cephalonica, mediates the 20-hydroxyecdysone (20E)-dependent acid phosphatase (ACP) activity at a nongenomic level. Affinity-purified polyclonal antibody against HP19 (alphaHP19-IgG) was used in the present study to understand the role of HP19 during the postembryonic development of Corcyra. In the in vitro studies, HP19 action was blocked either by immuno-precipitation using alphaHP19-IgG, prior to its addition to the fat body culture or by the addition of the antibody directly to the culture, along with 20E and hemolymph containing HP19. The alphaHP19-IgG blocked the HP19-mediated 20E-dependent ACP activation. In the in vivo studies, the alphaHP19-IgG was injected into the fully developed last (final/Vth) instar larvae of Corcyra, to complex the HP19 in vivo, in order to block the action of HP19. The injection of alphaHP19-IgG resulted in defective development of larvae, which grew either into non-viable larvae or larval-pupal/pupal-adult intermediates relative to the effect of pre-immune IgG injected controls. The present study shows that HP19 plays an important role in controlling the metamorphosis of Corcyra by regulating the 20E-dependent ACP activity. Coupled with the earlier findings, the ecdysteroid hormone regulates this action at a nongenomic level. PMID:17694564

  7. EFFECTS OF SUPPLEMENTAL LYSINE ON PERFORMANCE, ANTIBODY TITER AND RECTAL TEMPERATURE IN RESPONSE TO A MODIFIED-LIVE VIRAL VACCINE IN NEONATAL CALVES

    Directory of Open Access Journals (Sweden)

    Kate Sharon

    2014-01-01

    Full Text Available Infectious Bovine Rhinotracheitis (IBR, caused by bovine herpesvirus-1, contributes significantly to economic losses in the dairy and beef cattle industry. Lysine has been shown reduce virulence of herpesviruses in felids and humans. Our objective was to evaluate the effects of supplemental lysine on serum IBR antibody titer and rectal temperature in response to a modified-live Intranasal (IN or Intramuscular (IM respiratory-virus vaccination. Sixty-four neonatal Holstein bull calves (7±2 d of age; BW = 37±4.2 kg were used in a completely randomized design. Calves were fed milk replacer supplemented with either 17 g/d L-lysine monohydrochloride (LYS; 28 calves or an equivalent amount of casein (CAS; 28 calves for 42 d. Calves were then vaccinated with either an IN IBR-Parainfluenza virus-3 (PI3 or an IM (IBR-PI3-bovine viral diarrhea type I and II, bovine respiratory syncytial virus modified-live vaccine on d 36. A control group (8 calves received no supplement or vaccination. All calves were housed in individual calf pens (1.2×2.1 m. Daily feed intakes were monitored and BW measured weekly. Calves were bled on d 0, 35, 36, 37 and 42. Temperature data loggers were attached to rectal probes and temperatures were recorded every 5 min from d 28 to d 42. No significant differences were determined for average performance, rectal temperature, or IBR antibody titers with either IN or IM vaccinations between LYS and CAS treated calves (p>0.10. However, serum urea nitrogen and the ratio of serum lysine: Arginine increased (p<0.05 for LYS compared to CAS calves. These results suggest that supplementing lysine impacts nitrogen metabolism but does not alter the response to IBR vaccination or animal performance in neonatal Holstein calves.

  8. Polyclonal anti-idiotypic antibodies mimicking the small cell lung carcinoma antigen cluster-5A interact with a panel of antibodies and induce specific immune response in animals.

    OpenAIRE

    Zwicky, C.; Stahel, R A; Jaksche, H.; Waibel, R.; Lehmann, H. P.; Loibner, H

    1991-01-01

    Polyclonal anti-idiotypic antibodies (ab2) were generated by immunising goats with the murine IgG2a monoclonal antibody SWA20 which recognises the SCLC antigen cluster-5A, a tumour-associated sialoglycoprotein. Ab2 was shown to bind specifically to antibody SWA20, but not to isotype matched control antibodies. Pre-incubation with ab2 completely inhibited target cell binding of antibody SWA20 and of four other antibodies to cluster-5A antigen, while no effect was seen with antibodies to cluste...

  9. Antibody Peptide Based Antifungal Immunotherapy

    OpenAIRE

    Magliani, Walter; Conti, Stefania; Giovati, Laura; Zanello, Pier Paolo; Sperindè, Martina; Ciociola, Tecla; Polonelli, Luciano

    2012-01-01

    Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast kill...

  10. Antibody discovery: sourcing of monoclonal antibody variable domains.

    Science.gov (United States)

    Strohl, William R

    2014-03-01

    Historically, antibody variable domains for therapeutic antibodies have been sourced primarily from the mouse IgG repertoire, and typically either chimerized or humanized. More recently, human antibodies from transgenic mice producing human IgG, phage display libraries, and directly from human B lymphocytes have been used more broadly as sources of antibody variable domains for therapeutic antibodies. Of the total 36 antibodies approved by major maket regulatory agencies, the variable domain sequences of 26 originate from the mouse. Of these, four are marketed as murine antibodies (of which one is a mouse-rat hybrid IgG antibody), six are mouse-human chimeric antibodies, and 16 are humanized. Ten marketed antibodies have originated from human antibody genes, three isolated from phage libraries of human antibody genes and seven from transgenic mice producing human antibodies. Five antibodies currently in clinical trials have been sourced from camelids, as well as two from non-human primates, one from rat, and one from rabbit. Additional sources of antibody variable domains that may soon find their way into the clinic are potential antibodies from sharks and chickens. Finally, the various methods for retrieval of antibodies from humans, mouse and other sources, including various display technologies and amplification directly from B cells, are described. PMID:24168292

  11. Distinctive effects of CD34- and CD133-specific antibody-coated stents on re-endothelialization and in-stent restenosis at the early phase of vascular injury

    OpenAIRE

    Wu, Xue; Yin, Tieying; Tian, Jie; Tang, Chaojun; Huang, Junli; Zhao, Yinping; Zhang, Xiaojuan; Deng, Xiaoyan; Fan, Yubo; Yu, Donghong; Wang, Guixue

    2015-01-01

    It is not clear what effects of CD34- and CD133-specific antibody-coated stents have on re-endothelialization and in-stent restenosis (ISR) at the early phase of vascular injury. This study aims at determining the capabilities of different coatings on stents (e.g. gelatin, anti-CD133 and anti-CD34 antibodies) to promote adhesion and proliferation of endothelial progenitor cells (EPCs). The in vitro study revealed that the adhesion force enabled the EPCs coated on glass slides to withstand flo...

  12. Therapeutic effect of anti-TNF-alpha antibody and levofloxacin (LVFX) in a mouse model of enterohemorrhagic Escherichia coli O157 infection.

    Science.gov (United States)

    Isogai, E; Isogai, H; Hirose, K; Kubota, T; Kimura, K; Fujii, N; Hayashi, S; Takeshi, K; Oguma, K

    2001-10-01

    The ability of an anti-TNF-alpha antibody to confer protection against enterohaemorrhagic Escherichia coli (EHEC) O157 was investigated in germfree IQI mice. The use of an antibiotic levofloxacin (LVFX) alone or with the antibody was also studied. Protection included an increase in survival rate. Treatment with the anti-TNF-alpha antibody inhibited the histological signs associated with EHEC infection but did not prevent the colonization of EHEC or production of Shiga toxin (Stx). No clinical signs were observed and EHEC was completely eliminated in the mouse model receiving both anti-TNF-alpha antibody and LVFX. Anti-TNF-alpha antibody suppressed inflammatory cytokine response in the mouse kidney and brain by EHEC infection. PMID:11561957

  13. Monoclonal Antibodies Attached to Carbon Nanotube Transistors for Paclitaxel Detection

    Science.gov (United States)

    Lee, Wonbae; Lau, Calvin; Richardson, Mark; Rajapakse, Arith; Weiss, Gregory; Collins, Philip; UCI, Molecular Biology; Biochemistry Collaboration; UCI, Departments of Physics; Astronomy Collaboration

    Paclitaxel is a naturally-occurring pharmaceutical used in numerous cancer treatments, despite its toxic side effects. Partial inhibition of this toxicity has been demonstrated using weakly interacting monoclonal antibodies (3C6 and 8A10), but accurate monitoring of antibody and paclitaxel concentrations remains challenging. Here, single-molecule studies of the kinetics of antibody-paclitaxel interactions have been performed using single-walled carbon nanotube field-effect transistors. The devices were sensitized with single antibody attachments to record the single-molecule binding dynamics of paclitaxel. This label-free technique recorded a range of dynamic interactions between the antibody and paclitaxel, and it provided sensitive paclitaxel detection for pM to nM concentrations. Measurements with two different antibodies suggest ways of extending this working range and uncovering the mechanistic differences among different antibodies.

  14. Radiolabelled antibodies in imaging

    International Nuclear Information System (INIS)

    Recent technological advances make it possible to produce pure (monoclonal) antibodies in unlimited quantities without the need for continuous immunization of animals and to label these antibodies with a variety of radionuclides which can be traced by single-photon computed tomography. An outline review of the state of the art is presented, with particular reference to the imaging of myocardial infarcts and to tumour imaging studies using labelled monoclonal antibodies (sup(99m)Tc and 125I). Lengthy bibliography. (U.K.)

  15. Flow cytometry-based assay to evaluate human serum MUC1-Tn antibodies

    DEFF Research Database (Denmark)

    Van Elssen, Catharina H M J; Clausen, Henrik; Germeraad, Wilfred T V;

    2011-01-01

    detect antibodies binding to the underglycosylated MUC1 protein. This cellular system is complementary to the previously published methods to detect MUC1 serum antibodies, since the antibodies to the native protein are evaluated and therefore it can be effectively used for MUC1 antibody monitoring in...

  16. Single-domain antibodies for brain targeting

    OpenAIRE

    Lalatsa, Katerina; Moreira Leite, Diana

    2014-01-01

    Smaller recombinant antibody fragments as single-domain antibodies (sdAbs) are emerging as credible alternatives because of their target specificity, high affinity, and cost-effective recombinant production. sdAbs have been forged into multivalent and multispecif ic therapeutics, or targeting moieties, that are able to shuttle their linked therapeutic cargo (i.e., drugs, nanoparticles, toxins, enzymes, and radionuclides) to the receptor of interest. Their ability to permeate across the blood ...

  17. Clearance of pathological antibodies using biomimetic nanoparticles

    OpenAIRE

    Copp, Jonathan A.; Fang, Ronnie H.; Luk, Brian T.; Hu, Che-Ming J.; Gao, Weiwei; Zhang, Kang; Zhang, Liangfang

    2014-01-01

    The selective depletion of disease-causing antibodies using nanoparticles offers a new model in the management of type II immune hypersensitivity reactions. The demonstration of pathophysiologically inspired nanoengineering serves as a valuable prototype for additional therapeutic improvements with the goal of minimizing therapy-related adverse effects. Through the use of cell membrane-cloaked nanoparticles, nanoscale decoys with strong affinity to pathological antibodies can be administered ...

  18. The effect of infliximab, a monoclonal antibody against TNF-alpha, on disc herniation resorption - A randomized controlled study

    NARCIS (Netherlands)

    Autio, Reijo A.; Karppinen, Jaro; Niinimaki, Jaakko; Ojala, Risto; Veeger, Nic; Korhonen, Timo; Hurri, Heikki; Tervonen, Osmo

    2006-01-01

    Study Design. Randomized, controlled study. Objective. To evaluate the effect of infliximab on herniated nucleus pulposus (HNP) resorption. Summary of Background Data. Although the effects of tumor necrosis factor alpha (TNF-alpha) on HNP resorption are not fully understood, TNF-alpha appears to be

  19. Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

    Energy Technology Data Exchange (ETDEWEB)

    Paz-Filho, G.J.; Mesa-Junior, C.O.; Boguszewski, C.L.; Carvalho, G.A.; Graf, H. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Endocrinologia e Metabologia; Olandoski, M. [Pontificia Univ. Catolica do Parana, Curitiba, PR (Brazil). Nucleo de Bioestatistica; Woellner, L.C. [Centro de Medicina Nuclear, Curitiba, PR (Brazil); Goedert, C.A. [Centro de Tomografia Computadorizada, Curitiba, PR (Brazil)

    2007-12-15

    Recombinant human thyroid-stimulating hormone (rhTSH) enhances {sup 131}I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi {sup 131}I, in patients with MNG. Seventeen patients (15 females, 59.0 {+-} 13.1 years), who had never been submitted to {sup 131}I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi {sup 131}I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 {+-} 64.4 mL. {sup 131}I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean {sup 131}I 24-h uptake increased from 18.1 {+-} 9.7 to 49.6 {+-} 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 {+-} 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 {+-} 0.48 ng/dL for free-T4, 204.61 {+-} 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 {+-} 14.3% after 6 months (P < 0.001) and by 46.0 {+-} 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of {sup 131}I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects. (author)

  20. Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

    Directory of Open Access Journals (Sweden)

    G.J. Paz-Filho

    2007-12-01

    Full Text Available Recombinant human thyroid-stimulating hormone (rhTSH enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG. Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 ± 13.1 years, who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 ± 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 ± 9.7 to 49.6 ± 13.4% (P < 0.001, a median 2.6-fold increase (1.2 to 9.2. Peak hormonal levels were 10.86 ± 5.44 mU/L for TSH (a median 15.5-fold increase, 1.80 ± 0.48 ng/dL for free-T4, 204.61 ± 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%, painful thyroiditis (29.4% and hypothyroidism (52.9%. Thyroid volume was reduced by 34.3 ± 14.3% after 6 months (P < 0.001 and by 46.0 ± 14.6% after 1 year (P < 0.001. Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

  1. Anti-sulfotyrosine antibodies

    Science.gov (United States)

    Bertozzi, Carolyn R.; Kehoe, John; Bradbury, Andrew M.

    2009-09-15

    The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

  2. HIV Antibody Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? HIV Antibody and HIV Antigen (p24) Share this page: Was this page helpful? Also known as: HIV Screening Tests; AIDS Test; AIDS Screen; HIV Serology; ...

  3. Antinuclear antibody panel

    Science.gov (United States)

    ... blood may be due to: Chronic liver disease Collagen vascular disease Drug-induced lupus erythematosus Myositis (inflammatory muscle disease) ... Saunders; 2011:chap 51. Read More Antibody Arthritis Collagen vascular disease Drug-induced lupus erythematosus Liver disease Scleroderma Systemic ...

  4. PRODUCTION OF MONOCLONAL ANTIBODIES

    Directory of Open Access Journals (Sweden)

    TOLKOVA E.S.

    2015-01-01

    Full Text Available The article considers the use of monoclonal antibodies in immunotherapy and immunodiagnostics of oncological diseases and their production using hybridoma technolody with flow diagram and technological scheme of manufacturing process

  5. PRODUCTION OF MONOCLONAL ANTIBODIES

    OpenAIRE

    TOLKOVA E.S.

    2015-01-01

    The article considers the use of monoclonal antibodies in immunotherapy and immunodiagnostics of oncological diseases and their production using hybridoma technolody with flow diagram and technological scheme of manufacturing process

  6. Expression of Recombinant Antibodies

    OpenAIRE

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transg...

  7. [The biological significance of the genetically determined Se-se human blood group and its effect on the antibody formation process in donors immunized with staphylococcal anatoxin].

    Science.gov (United States)

    Patoka, V V

    1999-01-01

    82 blood donors have been observed, 63 of them were immunized. Blood group ABO(H), secreting group Se--se and Staphylococcus antibody contents (anti-alpha-staphylolysins) were determined in all the donors. It was found out that the donors-secretors with A(II) blood group exhibited the antibody-production increasing. It is supposed that the secreting of group-specific substance A, that has structural elements similar those of staphylococcus into saliva promotes antibody production increase against staphylococcus. The mechanism of such specific stimulation remains to be unknown and requires further studying. PMID:10687067

  8. Effects of different levels of hemp seed (Cannabis sativa L. and dextran oligosaccharide on growth performance and antibody titer response of broiler chickens

    Directory of Open Access Journals (Sweden)

    Mohammad Mahmoudi

    2015-03-01

    Full Text Available A total of 384 Ross 308 male broilers were used in a randomised complete design for a period of six weeks. The experiment was conducted as a 4×2 factorial arrangement with 4 levels of hemp seed (HS (0, 25, 50 and 75 g/kg and 2 levels of dextran oligossacharide (DOS (0 and 1 g/kg. Each of the 8 dietary treatments was fed to 4 replicate pens (12 birds/pen from 1 to 42 d of age. The results indicated that diets containing 25 g/kg HS caused significant decrease in average daily feed intake and average daily gain (ADG, whereas total serum cholesterol, low and very low density lipoprotein, and TG levels was minimised at 75 g/kg of HS, but serum high density lipoprotein (HDL was increased with increasing HS levels (P<0.01. Addition of 1 g/kg DOS diets compared with control diet, significantly increased ADG and HDL, and improved feed conversion ratio (P<0.05. Dietary DOS and HS had no significant effect on complete blood count, antibody production and relative weight of bursa and spleen in broilers (P>0.05. In conclusion, dietary HS and DOS can be used at their highest levels tested in the present study (75 g/kg of HS+1 g/kg of DOS to decrease lipid levels of blood serum in broilers without any negative effect on performance.

  9. The antibody mining toolbox: an open source tool for the rapid analysis of antibody repertoires.

    Science.gov (United States)

    D'Angelo, Sara; Glanville, Jacob; Ferrara, Fortunato; Naranjo, Leslie; Gleasner, Cheryl D; Shen, Xiaohong; Bradbury, Andrew R M; Kiss, Csaba

    2014-01-01

    In vitro selection has been an essential tool in the development of recombinant antibodies against various antigen targets. Deep sequencing has recently been gaining ground as an alternative and valuable method to analyze such antibody selections. The analysis provides a novel and extremely detailed view of selected antibody populations, and allows the identification of specific antibodies using only sequencing data, potentially eliminating the need for expensive and laborious low-throughput screening methods such as enzyme-linked immunosorbant assay. The high cost and the need for bioinformatics experts and powerful computer clusters, however, have limited the general use of deep sequencing in antibody selections. Here, we describe the AbMining ToolBox, an open source software package for the straightforward analysis of antibody libraries sequenced by the three main next generation sequencing platforms (454, Ion Torrent, MiSeq). The ToolBox is able to identify heavy chain CDR3s as effectively as more computationally intense software, and can be easily adapted to analyze other portions of antibody variable genes, as well as the selection outputs of libraries based on different scaffolds. The software runs on all common operating systems (Microsoft Windows, Mac OS X, Linux), on standard personal computers, and sequence analysis of 1-2 million reads can be accomplished in 10-15 min, a fraction of the time of competing software. Use of the ToolBox will allow the average researcher to incorporate deep sequence analysis into routine selections from antibody display libraries. PMID:24423623

  10. Passive antibody transfer in chickens to model maternal antibody after avian influenza vaccination.

    Science.gov (United States)

    Faulkner, Olivia B; Estevez, Carlos; Yu, Qingzhong; Suarez, David L

    2013-04-15

    Birds transfer maternal antibodies (MAb) to their offspring through the egg yolk where the antibody is absorbed and enters the circulatory system. Maternal antibodies provide early protection from disease, but may interfere with the vaccination efficacy in the chick. MAb are thought to interfere with vaccine antigen processing that reduces the subsequent immune response. Once MAb titers are depleted, the chick will respond to vaccination, but they are also susceptible to viral infection. This study examines the effect of MAb on seroconversion to different viral-vectored avian influenza virus (AIV) vaccines. Chicks were given passively transferred antibodies (PTA) using AIV hyperimmunized serum, and subsequently vaccinated with a fowlpox-AIV recombinant vaccine (FPr) or a Newcastle disease virus-AIV recombinant vaccine (NDVr). Our results indicate that passively transferred antibodies led to significant reduction of seroconversion and clinical protection from virulent challenge in recombinant virus vaccinated chicks thus demonstrating maternal antibody interference to vaccination. The passive antibody transfer model system provides an important tool to evaluate maternal antibody interference to vaccination. PMID:23398721

  11. Antibody deficiency in Rubinstein-Taybi syndrome.

    Science.gov (United States)

    Herriot, R; Miedzybrodzka, Z

    2016-03-01

    The developmental disorder Rubinstein-Taybi syndrome (RTS) is frequently complicated by recurrent respiratory infections. In many cases this is likely to be the result of microaspiration or gastro-oesophageal reflux but, in a proportion, underlying antibody deficiency is a potentially modifiable susceptibility factor for infection. Relatively subtle, specific defects of pneumococcal antibody production have previously been described in the context of RTS. Here, we report a rare association between the syndrome and an overt, major primary antibody deficiency disorder (common variable immune deficiency) which was successfully managed with immunoglobulin replacement therapy. Early recognition and investigation for antibody deficiency associated with RTS allied to effective and optimized treatment are essential to minimize morbidity and mortality and improve quality and duration of life. PMID:26307339

  12. Beneficial Effects of Anti-Interleukin-6 Antibodies on Impaired Gastrointestinal Motility, Inflammation and Increased Colonic Permeability in a Murine Model of Sepsis Are Most Pronounced When Administered in a Preventive Setup.

    Directory of Open Access Journals (Sweden)

    Sara Nullens

    Full Text Available During sepsis, gastrointestinal ileus, mucosal barrier dysfunction and bacterial translocation are accepted to be important triggers that can maintain or exacerbate the septic state. In the caecal ligation and puncture animal model of sepsis, we demonstrated that systemic and colonic interleukin-6 levels are significantly increased coinciding with an impaired colonic barrier function. We therefore aimed to study the effect of therapeutic or curative administration of anti-IL6 antibodies on overall GI motility, colonic permeability and translocation of intestinal bacteria in blood and mesenteric lymph nodes in the mouse caecal ligation and puncture model.OF-1 mice were randomized to either the preventive or curative protocol, in which they received 1 mg/kg of antibodies to interleukin-6, or its IgG isotype control solution. They subsequently underwent either the caecal ligation and puncture procedure, or sham-surgery. GI motility was assessed 48 h following the procedure, as well as colonic permeability, serum and colon cytokines, colonic tight junction proteins at the mRNA level; cultures of blood and mesenteric lymph nodes were performed.Preventive administration of anti-interleukin-6 antibodies successfully counteracted the gastrointestinal motility disturbances and impaired colonic barrier function that could be observed in vehicle-treated septic animals. Serum and colonic levels of proinflammatory cytokines were significantly lower when animals were preventively treated with anti-interleukin-6 antibodies. A repetitive injection 24 h later resulted in the most pronounced effects. Curative treatment significantly lowered systemic and colonic inflammation markers while the effects on transit and permeability were unfortunately no longer significant.Caecal ligation and puncture resulted in septic ileus with an increased colonic permeability. Antibodies to interleukin-6 were able to ameliorate gastro-intestinal motility, suppress inflammation and

  13. Chloroquine encapsulated in malaria-infected erythrocyte-specific antibody-bearing liposomes effectively controls chloroquine-resistant Plasmodium berghei infections in mice.

    OpenAIRE

    Owais, M; Varshney, G C; Choudhury, A.; S. Chandra; Gupta, C M

    1995-01-01

    The suitability of liposomes as drug carriers in the treatment of drug-resistant rodent malaria was examined after covalently attaching F(ab')2 fragments of a mouse monoclonal antibody (MAb), MAb F10, raised against the host cell membranes isolated from the Plasmodium berghei-infected mouse erythrocytes, to the liposome surface. The antibody-bearing liposomes thus formed specifically recognized the P. berghei-infected mouse erythrocytes under both in vitro and in vivo conditions. No such spec...

  14. Impact of chronic lymphocytic thyroiditis co-existing with differentiated thyroid cancer on the effectiveness of remnants ablation

    International Nuclear Information System (INIS)

    Full text: Some stages of chronic lymphocytic thyroiditis (CLT) are functionally characterized by an organification defect with large intra thyroid inorganic iodide pool, which can be discharged during perchlorate test. Fluorescent scan study indicates that most patients with CLT have decreased stable iodine store in the thyroid gland. The aim of our study was to investigate the possible consequences of these organification abnormalities during remnants ablation in patients with coexisting differentiated thyroid cancer (DTC) and chronic lymphocytic thyroiditis. We reviewed our series of patients of DTC being followed at the department of nuclear medicine of the university hospital Sahloul. Among the 350 patients with DTC, 30 (8.5%) had histologically proved chronic lymphocytic thyroiditis, with infiltration of the non-tumoral thyroid tissue. A second group of 60 patients (without evidence of lymphocytic infiltration) was selected randomly and used as control. The median of follow-up for these two groups was 4 years. All patients had undergone total thyroidectomy followed by scintigraphy 4-6 weeks later. In patients with thyroid remnants, standard ablative dose of 3.7 GBq of I-131 (100 mCi) was administrated with 6 months duration between all therapies, until the negativity of thyroid bed activity on follow up survey scan performed 48 to 72 hours after administering 2 to 3 mCi of I-131. Thyroglobulin (Tg) serum level was not considered as a criterion of ablation, because of the frequency of anti-thyroid antibodies in CLT. In the group with CLT, 3 patients had negative postoperative neck scintigraphy. Complete ablation was achieved with a single standard dose in 14, two standard doses in 5, and more than 200 mCi in two patients (300 in one and 400 in two). In five patients, ablation is not yet achieved. In the control group, ablation was obtained with 100 mCi in 43 patients, 200 mCi in 9, and 300 mCi in 3. In five patients ablation has not been achieved. Considering

  15. Monoclonal antibodies in targeted therapy

    Directory of Open Access Journals (Sweden)

    Beata Powroźnik

    2012-09-01

    Full Text Available Targeted therapy is a new therapeutic method consisting in the inhibition of specific molecular pathways. In modern therapy, the key role is played by monoclonal antibodies, included in the group of biological agents. The success of molecularly targeted therapy is to define the proper “molecular target”, selecting the right drug active against a specific “target” and selecting a group of patients who benefit from treatment. Introduction of targeted therapy resulted in improved results of the treatment of many serious and chronic diseases. In general, targeted molecular therapies have good toxicity profiles, but some patients are exquisitely sensitive to these drugs and can develop particular and severe toxicities. Patient selection and proper monitoring significantly decrease the risk of life-threatening adverse events. Data concerning late side effects are still unavailable because of the short follow-up of molecularly targeted therapy. Currently in the U.S. and Europe there are approximately 31 registered therapeutic monoclonal antibodies, while 160 are subjected to clinical trials. This paper presents an overview of therapeutic monoclonal antibodies currently used in therapy and the present state of knowledge about them. 

  16. Effect of isologous and autologous insulin antibodies on in vivo bioavailability and metabolic fate of immune-complexed insulin in Lou/M rats

    International Nuclear Information System (INIS)

    The in vivo bioavailability, distribution, and metabolic fate of 125I-labeled insulin complexed to isologous and autologous antibodies were studied in inbred Lou/M rats. There was an impaired bioavailability of the 125I-insulin bound to the isologous and autologous antibodies. Very little of the 125I-insulin in these immune complexes could bind to insulin receptors on hepatocytes or renal tubular cells and be degraded, because the amounts of 125I from degraded 125I-insulin in the blood or secreted into the stomach were markedly attenuated in both cases for at least 30 min after injection. There was a simultaneous accumulation of 125I-insulin immune complexes in the liver and the kidneys of Lou/M rats injected with 125I-insulin complexed with isologous antibodies or when insulin-immunized Lou/M rats were injected with 125I-insulin during the same interval. The impaired bioavailability of immune-complexed insulin and altered distribution of radioactivity due to the accumulation of immune complexes in the liver and kidney were also observed in previous experiments in which Lewis rats were injected with xenogenic guinea pig and homologous insulin antibodies. These observations are therefore submitted as evidence that the Lou/M rat is a valid model in which to study the bioavailability of insulin immune complexed to isologous, homologous, and xenogenic antibodies and the metabolic fate of the respective insulin-antibody immune complexes

  17. Programmed Death-1 Antibody Blocks Therapeutic Effects of T-Regulatory Cells in Cockroach Antigen-Induced Allergic Asthma

    OpenAIRE

    McGee, Halvor S; Yagita, Hideo; Shao, Zhifei; Devendra K Agrawal

    2009-01-01

    We recently reported that the adoptive transfer of T-regulatory cells (Tregs) isolated from lung and spleen tissue of green fluorescent protein–transgenic mice reversed airway hyperresponsiveness and airway inflammation. Because Programmed Death-1 (PD-1) is a pivotal receptor regulating effector T-cell activation by Tregs, we evaluated whether PD-1 is involved in the therapeutic effect of naturally occurring Tregs (NTregs) and inducible Tregs (iTregs) in cockroach (CRA)-sensitized and challen...

  18. Milk supplemented with immune colostrum: protection against rotavirus diarrhea and modulatory effect on the systemic and mucosal antibody responses in calves experimentally challenged with bovine rotavirus.

    Science.gov (United States)

    Parreño, V; Marcoppido, G; Vega, C; Garaicoechea, L; Rodriguez, D; Saif, L; Fernández, F

    2010-07-01

    Group A bovine rotavirus (BRV) is the major cause of neonatal calf diarrhea worldwide. As a preventive strategy, we evaluated the protection and immunomodulation in two groups of BRV-inoculated calves. All calves received control colostrum (CC; VN=65,536; IgG(1)=16,384) prior to gut closure followed by the milk supplemented with immune colostrum (VN=1,048,576; IgG(1)=262,144), twice a day, for 14 days. Calves received milk supplemented with 0.8% immune colostrum [(Gp 1) VN=16,384; IgG(1)=4096] or milk supplemented with 0.4% immune colostrum [(Gp 2) VN=1024; IgG(1)=1024]. Calves receiving CC or colostrum deprived calves (CD) fed antibody (Ab) free milk served as controls (Gp 3 and 4). Calves were inoculated with virulent BRV IND at 2 days of age. Group 1 calves (milk IgG(1) 4096) showed 80% protection against BRV diarrhea and significantly reduced virus shedding. At 21 post-inoculation days (PID), the antibody secreting cell (ASC) responses of Gp 1 calves were limited mainly to duodenal and jejunal lamina propria (LP) with limited or no responses in systemic sites (spleen and PBL) and mesenteric lymph nodes. The profile of serum and fecal Ab responses as well as the ASC responses was also modulated by the presence of passive IgG(1) Abs and probably other colostrum components, toward higher titers of IgA Ab in serum and feces and a greater number of IgA ASC in the proximal intestine, reflecting positive modulation by colostrum toward this isotype associated with optimal protection of the intestinal mucosa. After challenge, at PID 21, all calves in Gp 1 and 2 were fully protected against diarrhea and only 1 of 5 calves in Gp 1 shed virus asymptomatically, indicating that the passive Ab treatment for 14 days was effective in protecting most of the animals after a first and a second virus exposure. The final outcome was a positive modulation of the mucosal immune responses and a high protection rate against diarrhea and virus shedding during the period of peak

  19. Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers

    Directory of Open Access Journals (Sweden)

    Laine J

    2016-04-01

    Full Text Available Juha Laine,1 T Sakari Jokiranta,2,3 Kari K Eklund,4,5 Merja Väkeväinen,1 Kari Puolakka6 1Pfizer Oy, Helsinki, 2United Medix Laboratories Ltd, Espoo, 3Research Programs Unit, Immunobiology, 4Department of Rheumatology, University of Helsinki, 5Helsinki University Central Hospital, Helsinki, 6Department of Medicine, South Karelia, Finland Abstract: Monitoring of anti-drug antibodies (ADAbs or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3–6 months scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2–5 of 100 patients, a proportion which is easily

  20. Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model

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    Megas Françoise

    2010-03-01

    Full Text Available Abstract Background Antibodies directed against haemagglutinin, measured by the haemagglutination inhibition (HI assay are essential to protective immunity against influenza infection. An HI titre of 1:40 is generally accepted to correspond to a 50% reduction in the risk of contracting influenza in a susceptible population, but limited attempts have been made to further quantify the association between HI titre and protective efficacy. Methods We present a model, using a meta-analytical approach, that estimates the level of clinical protection against influenza at any HI titre level. Source data were derived from a systematic literature review that identified 15 studies, representing a total of 5899 adult subjects and 1304 influenza cases with interval-censored information on HI titre. The parameters of the relationship between HI titre and clinical protection were estimated using Bayesian inference with a consideration of random effects and censorship in the available information. Results A significant and positive relationship between HI titre and clinical protection against influenza was observed in all tested models. This relationship was found to be similar irrespective of the type of viral strain (A or B and the vaccination status of the individuals. Conclusion Although limitations in the data used should not be overlooked, the relationship derived in this analysis provides a means to predict the efficacy of inactivated influenza vaccines when only immunogenicity data are available. This relationship can also be useful for comparing the efficacy of different influenza vaccines based on their immunological profile.

  1. Glycosylation of recombinant human thyroid peroxidase ectodomain of insect cell origin has little effect on recognition by serum thyroid peroxidase antibody

    Institute of Scientific and Technical Information of China (English)

    LIU Ming-ming; LI Qing; ZHAO Lan-lan; GAO Ying; HUANG You-yuan; LU Gui-zhi; GAO Yan-ming

    2013-01-01

    Background Thyroid peroxidase (TPO) is an important autoantigen in Hashimoto's thyroiditis (HT),and almost all epitopes are located in TPO ectodomain.The glycosylation of TPO might contribute to breaking self-tolerance,therefore,purified glycosylated recombinant TPO ectodomain is prerequisite of elucidating its role in the pathogenesis of HT.The aim of our study was to investigate whether the glycosylation has influence on the antigenic determinants of recombinant TPO.Methods Bac-to-Bac baculovirus expression system was used to generate recombinant human TPO ectodomain.The antigenicity was analyzed by antigen specific enzyme-linked immunosorbant assays (ELISAs).The glycosylation of recombinant human TPO ectodomain of High Five insect cell origin was detected by lectin-ELISAs.Results TPO ectodomain was recovered from the culture media as a soluble protein,and it was fused with a hexahistidine tag which allowed purification by nickel-affinity chromatography.The recombinant TPO ectodomain could be recognized by all the 54 HT patients and three TPO monoclonal antibodies.Fucose,sialic acid and galactose were all detected on the recombinant TPO ectodomain.Sera TPOAb binding decreased slightly after non-specific deglycosylation of TPO by periodic acid.Conclusions High Five insect cells derived recombinant human TPO ectodomain had N-glycosylation sites,which might have little effect on recognition by serum TPOAb.

  2. Effects of Thyroid Peroxidase Antibody on Maternal and Neonatal Outcomes in Pregnant Women in an Iodine-Sufficient Area in China

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    Xi Chen

    2016-01-01

    Full Text Available Purposes. To evaluate the effects of thyroid peroxidase antibodies (TPOAb on maternal and neonatal adverse outcomes in pregnant women. Methods. 208 pregnant women at 24–28 weeks were divided into two groups, TPOAb-positive and TPOAb-negative groups. Thyroid function and TPOAb were determined in all subjects until 12 months postpartum. Levothyroxine was supplemented to maintain euthyroid with periodical checking of thyroid functions. The prevalence of postpartum thyroiditis (PPT, placenta previa, placental abruption, premature rupture of membrane, postpartum haemorrhage, polyhydramnios, oligohydramnios, preterm birth, low birth weight, congenital hypothyroidism, and neonatal diseases were observed in two groups. Results. Of all women, 11.54% had a PPT. The prevalence of PPT was significantly higher in TPOAb-positive than TPOAb-negative group (42.31% versus 7.14%, P<0.001, with 45.46% and 53.85% of PPT happening at 6 weeks postpartum in TPOAb-positive and TPOAb-negative groups. The incidence of polyhydramnios was significantly higher in TPOAb-positive than TPOAb-negative group (15.38% versus 2.74%, P=0.02. Conclusion. Pregnant women with TPOAb-positive had increased risk of PPT, predominantly happening at 6 weeks postpartum. TPOAb was associated with increased incidence of polyhydramnios and the underlying mechanisms required further investigation. Earlier screening of thyroid function during pregnancy and postpartum was warranted in our region.

  3. Evaluation of the effects of systemic treatment with a sclerostin neutralizing antibody on bone repair in a rat femoral defect model.

    Science.gov (United States)

    Alaee, Farhang; Virk, Mandeep S; Tang, Hezhen; Sugiyama, Osamu; Adams, Douglas J; Stolina, Marina; Dwyer, Denise; Ominsky, Michael S; Ke, Hua Zhu; Lieberman, Jay R

    2014-02-01

    Systemic administration of a sclerostin neutralizing antibody (Scl-Ab) has been shown to enhance fracture callus density and strength in several animal models. In order to further evaluate the potential of Scl-Ab to improve healing in a bone defect model,we evaluated Scl-Ab in a 3mm femoral defect in young male outbred rats. Scl-Ab was given either continuously for 6 or 12 weeks after surgery or with 2 weeks of delay for 10 weeks. Bone formation was assessed by radiographs, µ-CT, and histology. Complete bony union was achieved in only a few defects after 12 weeks of healing (Scl-Ab treated 5/30, vehicle treated 1/15). µ-CT evaluation demonstrated a significant increase in the BV/TV in the defect in the delayed treatment group (65%, prepair in a bone defect and in the surrounding host bone, but lacks the osteoinductive activity to heal it. This agent seems to be most effective in bone repair scenarios where there is cortical integrity. PMID:24600701

  4. BRAF V600E Mutation as a Predictive Factor of Anti-EGFR Monoclonal Antibodies Therapeutic Effects in Metastatic Colorectal Cancer:a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    Jia Wei

    2014-01-01

    Objective To investigate the correlation between BRAF V600E mutation and anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs) therapeutic effects in metastatic colorectal cancer. Methods Studies were included into meta-analysis to investigate the association between BRAF V600E mutation and clinical outcome in metastatic colorectal cancer patients treated with anti-EGFR MoAbs. Results A total of 7 studies were included in this meta-analysis. The 7 studies included 1352 patients in total, sample sizes ranged from 67 to 493. Objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) were collected from included studies and were used to assess the strength of the relation. In patients with wild-type KRAS, the pooled odds ratio for ORR of mutant BRAF over wild-type BRAF was 0.27 (95%CI=0.10-0.70). BRAF mutation predicted a deterioration in PFS and OS in wild-type KRAS patients treated with anti-EGFR MoAbs (hazard ratio=2.78, 95% CI=1.62-4.76;hazard ratio=2.54, 95%CI=1.93-3.32). Conclusion BRAF V600E mutation is related to lack of response and worse survival in wild-type KRAS metastatic colorectal cancer patients treated with anti-EGFR MoAbs.

  5. Effects of Thyroid Peroxidase Antibody on Maternal and Neonatal Outcomes in Pregnant Women in an Iodine-Sufficient Area in China.

    Science.gov (United States)

    Chen, Xi; Jin, Bai; Xia, Jun; Tao, Xincheng; Huang, Xiaoping; Sun, Lu; Yuan, Qingxin

    2016-01-01

    Purposes. To evaluate the effects of thyroid peroxidase antibodies (TPOAb) on maternal and neonatal adverse outcomes in pregnant women. Methods. 208 pregnant women at 24-28 weeks were divided into two groups, TPOAb-positive and TPOAb-negative groups. Thyroid function and TPOAb were determined in all subjects until 12 months postpartum. Levothyroxine was supplemented to maintain euthyroid with periodical checking of thyroid functions. The prevalence of postpartum thyroiditis (PPT), placenta previa, placental abruption, premature rupture of membrane, postpartum haemorrhage, polyhydramnios, oligohydramnios, preterm birth, low birth weight, congenital hypothyroidism, and neonatal diseases were observed in two groups. Results. Of all women, 11.54% had a PPT. The prevalence of PPT was significantly higher in TPOAb-positive than TPOAb-negative group (42.31% versus 7.14%, P polyhydramnios was significantly higher in TPOAb-positive than TPOAb-negative group (15.38% versus 2.74%, P = 0.02). Conclusion. Pregnant women with TPOAb-positive had increased risk of PPT, predominantly happening at 6 weeks postpartum. TPOAb was associated with increased incidence of polyhydramnios and the underlying mechanisms required further investigation. Earlier screening of thyroid function during pregnancy and postpartum was warranted in our region. PMID:26884759

  6. The labelling of adriamycin-loaded human serum albumin immuno-nanoparticles led by monoclonal antibodies with 131I and its anti-hepatoma effect in vivo

    International Nuclear Information System (INIS)

    The pharmaceutics character, targeting to hepatoma and anticancer activity in nude mice of adriamycin-loaded human serum albumin immuno-nanoparticles (ADR-HSA-NP) against hepatoma led by anti-human hepatoma monoclonal antibodies HAb18 are studied. The results show that effective loaded drug dose of HAb18-ADR-HSA-NP is 1.44%, which is lower than ADR-HSA-NP (1.69%); HAb18-ADR-HSA-NP slowly releases drug ADR and its maximum releasing drug dose (41%) is obviously lower than ADR-HSA-NP (65%) (P 131I-HAb18-ADR-HSA-NP mainly accumulates in liver and its liver-taxis and stability are better than 131I-ADR-HSA-NP in nude mice by intravenous injection; HAb18-ADR-HSA-NP mainly accumulates in tumor and its accumulation amount of tumor is higher than ADR-HSA-NP (P < 0.05), and has obvious inhibiting cancer action and its inhibitory rate of cancer is also higher than ADR-HSA-NP (P < 0.05) by tumor injection. So, HAb18-ADR-HSA-NP can bind and inhibit hepatoma cell from growing in vivo

  7. Ameliorative effect of a microbial feed additive on infectious bronchitis virus antibody titer and stress index in broiler chicks fed deoxynivalenol.

    Science.gov (United States)

    Ghareeb, K; Awad, W A; Böhm, J

    2012-04-01

    Although acute mycotoxicoses are rare in poultry production, chronic exposure to low levels of mycotoxins is responsible for reduced productivity and increased susceptibility to infectious diseases. Deoxynivalenol (DON) is known to modulate immune function, but only a few studies have investigated the effect of DON on the vaccinal immune response. In addition, the effects of Mycofix select (Biomin GmbH, Herzogenburg, Austria) supplementation to DON-contaminated broiler diets have not yet been demonstrated. Therefore, an experiment with 1-d-old male broilers (Ross 308) was carried out to examine the effects of feeding DON-contaminated low-protein grower diets on performance, serum biochemical parameters, lymphoid organ weight, and antibody titers to infectious bronchitis vaccination in serum and to evaluate the effects of Mycofix select dietary supplementation in either the presence or absence of DON in broilers. In total, thirty-two 1-d-old broiler chicks were randomly assigned to 1 of the 4 dietary treatments for 5 wk. The dietary treatments were 1) control; 2) artificially contaminated diets with 10 mg of DON/kg of diet; 3) DON-contaminated diets supplemented with Mycofix select; and 4) control diet supplemented with Mycofix select. Feeding of contaminated diets decreased (P = 0.000) the feed intake, BW (P = 0.001), BW gain (P = 0.044), and feed efficiency during the grower phase. Deoxynivalenol affected the blood biochemistry, whereas plasma total protein and uric acid concentrations in birds fed contaminated grains were decreased compared with those of the controls. Moreover, in birds fed contaminated feeds, there was a tendency to reduce triglycerides in the plasma (P = 0.090), suggesting that DON in the diets affected protein and lipid metabolism in broiler chickens. The feeding of contaminated diets altered the immune response in broilers by reducing the total lymphocyte count. Similarly, the antibody response against infectious bronchitis vaccination

  8. Discovering neutralizing antibodies targeting the stem epitope of H1N1 influenza hemagglutinin with synthetic phage-displayed antibody libraries

    Science.gov (United States)

    Tung, Chao-Ping; Chen, Ing-Chien; Yu, Chung-Ming; Peng, Hung-Pin; Jian, Jhih-Wei; Ma, Shiou-Hwa; Lee, Yu-Ching; Jan, Jia-Tsrong; Yang, An-Suei

    2015-01-01

    Broadly neutralizing antibodies developed from the IGHV1–69 germline gene are known to bind to the stem region of hemagglutinin in diverse influenza viruses but the sequence determinants for the antigen recognition, including neutralization potency and binding affinity, are not clearly understood. Such understanding could inform designs of synthetic antibody libraries targeting the stem epitope on hemagglutinin, leading to artificially designed antibodies that are functionally advantageous over antibodies from natural antibody repertoires. In this work, the sequence space of the complementarity determining regions of a broadly neutralizing antibody (F10) targeting the stem epitope on the hemagglutinin of a strain of H1N1 influenza virus was systematically explored; the elucidated antibody-hemagglutinin recognition principles were used to design a phage-displayed antibody library, which was then used to discover neutralizing antibodies against another strain of H1N1 virus. More than 1000 functional antibody candidates were selected from the antibody library and were shown to neutralize the corresponding strain of influenza virus with up to 7 folds higher potency comparing with the parent F10 antibody. The antibody library could be used to discover functionally effective antibodies against other H1N1 influenza viruses, supporting the notion that target-specific antibody libraries can be designed and constructed with systematic sequence-function information. PMID:26456860

  9. PK/PD analysis of a novel pH-dependent antigen-binding antibody using a dynamic antibody-antigen binding model.

    Science.gov (United States)

    Haraya, Kenta; Tachibana, Tatsuhiko; Iwayanagi, Yuki; Maeda, Atsuhiko; Ozeki, Kazuhisa; Nezu, Junichi; Ishigai, Masaki; Igawa, Tomoyuki

    2016-04-01

    Previously, we have reported novel engineered antibody with pH-dependent antigen-binding (recycling antibody), and with both pH-dependent antigen-binding and increased FcRn-binding at neutral pH (sweeping antibody). The purpose of this study is to perform PK/PD predictions to better understand the potential applications of the antibodies as therapeutics. To demonstrate the applicability of recycling and sweeping antibodies over conventional antibodies, PK/PD analyses were performed. PK/PD parameters for antibody and antigen dynamics were estimated from the results of a pharmacokinetic study in human FcRn transgenic mice. A simulation study was performed using the estimated PK/PD parameters with various target antigen profiles. In comparison to conventional antibody, recycling antibody enhanced antibody-antigen complex clearance by 3 folds, while sweeping antibody accelerated antigen clearance by 10 folds in a pharmacokinetic study. Simulation results showed that recycling and sweeping antibodies can improve dosage frequency and reduce the required dose for target antigens with various clearances, plasma concentrations or binding kinetics. Moreover, importance of the association rate constant to enhance the beneficial effect of antibodies was shown. These results support the conclusion that recycling and sweeping antibodies can be applied to various target antigens with different profiles, and expand the number of antigens that antibodies can target. PMID:26944099

  10. In vivo effects of monoclonal anti-L3T4 antibody on immune responsiveness of mice infected with Schistosoma mansoni. Reduction of irradiated cercariae-induced resistance

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, E.A.; Colley, D.G.

    1988-04-15

    Mice can be partially protected against challenge infections of Schistosoma mansoni cercariae by either single or multiple exposure to irradiated cercariae (x-cerc). The participation of L3T4+ lymphocytes on this resistance phenomenon was evaluated by selectively depleting this cell population through in vivo administration of mAb anti-L3T4 at three different times in relationship to the challenge infections. Treatment with anti-L3T4 before challenge such that depletion was effective during the time of cercarial skin penetration and dermal/s.c. residence significantly reduced the level of resistance induced by x-cerc sensitization. When treatment was delayed until after challenge, depletion of L3T4+ cells coincided with either the lung or post-lung/liver phases of schistosomular migration, and normal levels of x-cerc-induced resistance were induced. In contrast to once-immunized mice, mice hyperimmunized by five exposures to x-cerc and then depleted of L3T4+ cells at the time of challenge still expressed resistance to the challenge. These data suggest that when mice are sensitized only once with x-cerc the challenge infection provides a necessary immunologic boost which requires L3T4+ cells for effective expression of resistance. The requirement for this anamnestic effect by the challenge infection can be circumvented by hyperimmunization. Evaluation of the immune response of one-time sensitized or hyperimmunized mice demonstrated that cellular Ag-specific proliferative responses and mitogen-induced lymphokine production were abrogated after any of the various in vivo regimens of anti-L3T4 antibody. In contrast, immunoblot analysis of humoral responsiveness revealed a correlation between the expression of resistance and the ability of sera from immunized and anti-L3T4 treated mice to recognize a 75-kDa parasite antigenic component.

  11. In vivo effects of monoclonal anti-L3T4 antibody on immune responsiveness of mice infected with Schistosoma mansoni. Reduction of irradiated cercariae-induced resistance

    International Nuclear Information System (INIS)

    Mice can be partially protected against challenge infections of Schistosoma mansoni cercariae by either single or multiple exposure to irradiated cercariae (x-cerc). The participation of L3T4+ lymphocytes on this resistance phenomenon was evaluated by selectively depleting this cell population through in vivo administration of mAb anti-L3T4 at three different times in relationship to the challenge infections. Treatment with anti-L3T4 before challenge such that depletion was effective during the time of cercarial skin penetration and dermal/s.c. residence significantly reduced the level of resistance induced by x-cerc sensitization. When treatment was delayed until after challenge, depletion of L3T4+ cells coincided with either the lung or post-lung/liver phases of schistosomular migration, and normal levels of x-cerc-induced resistance were induced. In contrast to once-immunized mice, mice hyperimmunized by five exposures to x-cerc and then depleted of L3T4+ cells at the time of challenge still expressed resistance to the challenge. These data suggest that when mice are sensitized only once with x-cerc the challenge infection provides a necessary immunologic boost which requires L3T4+ cells for effective expression of resistance. The requirement for this anamnestic effect by the challenge infection can be circumvented by hyperimmunization. Evaluation of the immune response of one-time sensitized or hyperimmunized mice demonstrated that cellular Ag-specific proliferative responses and mitogen-induced lymphokine production were abrogated after any of the various in vivo regimens of anti-L3T4 antibody. In contrast, immunoblot analysis of humoral responsiveness revealed a correlation between the expression of resistance and the ability of sera from immunized and anti-L3T4 treated mice to recognize a 75-kDa parasite antigenic component

  12. Effects of Cationic Microbubble Carrying CD/TK Double Suicide Gene and αVβ3 Integrin Antibody in Human Hepatocellular Carcinoma HepG2 Cells

    Science.gov (United States)

    Li, Jiale; Zhou, Ping; Li, Lan; Zhang, Yan; Shao, Yang; Tang, Li; Tian, Shuangming

    2016-01-01

    Objective Hepatocellular carcinoma (HCC), mostly derived from hepatitis or cirrhosisis, is one of the most common types of liver cancer. T-cell mediated immune response elicited by CD/TK double suicide gene has shown a substantial antitumor effect in HCC. Integrin αVβ3 over expresssion has been suggested to regulate the biology behavior of HCC. In this study, we investigated the strategy of incorporating CD/TK double suicide gene and anti-αVβ3 integrin monoclonal antibodies into cationic microbubbles (CMBsαvβ3), and evaluated its killing effect in HCC cells. Methods To improve the transfection efficiency of targeted CD/TK double suicide gene, we adopted cationic microbubbles (CMBs), a cationic delivery agent with enhanced DNA-carrying capacity. The ultrasound and high speed shearing method was used to prepare the non-targeting cationic microbubbles (CMBs). Using the biotin-avidin bridge method, αVβ3 integrin antibody was conjugated to CMBs, and CMBsαvβ3 was generated to specifically target to HepG2 cells. The morphology and physicochemical properties of the CMBsαvβ3 was detected by optical microscope and zeta detector. The conjugation of plasmid and the antibody in CMBsαvβ3 were examined by immunofluorescent microscopy and flow cytometry. The binding capacities of CMBsαvβ3 and CMBs to HCC HepG2 and normal L-02 cells were compared using rosette formation assay. To detect EGFP fluorescence and examine the transfection efficiencies of CMBsαvβ3 and CMBs in HCC cells, fluorescence microscope and contrast-enhanced sonography were adopted. mRNA and protein level of CD/TK gene were detected by RT-PCR and Western blot, respectively. To evaluate the anti-tumor effect of CMBsαvβ3, HCC cells with CMBsαvβ3 were exposed to 5-flurocytosine / ganciclovir (5-FC/GCV). Then, cell cycle distribution after treatment were detected by PI staining and flow cytometry. Apoptotic cells death were detected by optical microscope and assessed by MTT assay and TUNEL

  13. Effects of Cationic Microbubble Carrying CD/TK Double Suicide Gene and αVβ3 Integrin Antibody in Human Hepatocellular Carcinoma HepG2 Cells.

    Directory of Open Access Journals (Sweden)

    Jiale Li

    Full Text Available Hepatocellular carcinoma (HCC, mostly derived from hepatitis or cirrhosisis, is one of the most common types of liver cancer. T-cell mediated immune response elicited by CD/TK double suicide gene has shown a substantial antitumor effect in HCC. Integrin αVβ3 over expresssion has been suggested to regulate the biology behavior of HCC. In this study, we investigated the strategy of incorporating CD/TK double suicide gene and anti-αVβ3 integrin monoclonal antibodies into cationic microbubbles (CMBsαvβ3, and evaluated its killing effect in HCC cells.To improve the transfection efficiency of targeted CD/TK double suicide gene, we adopted cationic microbubbles (CMBs, a cationic delivery agent with enhanced DNA-carrying capacity. The ultrasound and high speed shearing method was used to prepare the non-targeting cationic microbubbles (CMBs. Using the biotin-avidin bridge method, αVβ3 integrin antibody was conjugated to CMBs, and CMBsαvβ3 was generated to specifically target to HepG2 cells. The morphology and physicochemical properties of the CMBsαvβ3 was detected by optical microscope and zeta detector. The conjugation of plasmid and the antibody in CMBsαvβ3 were examined by immunofluorescent microscopy and flow cytometry. The binding capacities of CMBsαvβ3 and CMBs to HCC HepG2 and normal L-02 cells were compared using rosette formation assay. To detect EGFP fluorescence and examine the transfection efficiencies of CMBsαvβ3 and CMBs in HCC cells, fluorescence microscope and contrast-enhanced sonography were adopted. mRNA and protein level of CD/TK gene were detected by RT-PCR and Western blot, respectively. To evaluate the anti-tumor effect of CMBsαvβ3, HCC cells with CMBsαvβ3 were exposed to 5-flurocytosine / ganciclovir (5-FC/GCV. Then, cell cycle distribution after treatment were detected by PI staining and flow cytometry. Apoptotic cells death were detected by optical microscope and assessed by MTT assay and TUNEL

  14. Effects of a Formula Containing Two Types of Prebiotics, Bifidogenic Growth Stimulator and Galacto-oligosaccharide, and Fermented Milk Products on Intestinal Microbiota and Antibody Response to Influenza Vaccine in Elderly Patients: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Shinya Nagafuchi

    2015-06-01

    Full Text Available We investigated the effect of a formula containing two different prebiotics (bifidogenic growth stimulator and galacto-oligosaccharide and fermented milk products on intestinal microbiota and antibody responses to an influenza vaccine in enterally fed elderly in-patients. Patients were administered either formula containing prebiotics and fermented milk products (group F: n = 12, 79.9 ± 9.5 years old or standard formula (group C: n = 12, 80.7 ± 10.1 years old via percutaneous endoscopic gastrostomy during a 14-week intervention period. Subjects were immunized with an influenza vaccine (A/H1N1, A/H3N2, and B at week 4 of the intervention. Blood biochemical indices, intestinal bacteria populations and antibody titers were analyzed. Bifidobacterium counts increased significantly in group F compared with group C. The enhanced antibody titers against A/H1N1 were maintained in group F for a longer period compared with group C. The titers against A/H3N2 were unchanged between both groups, and those against B were significantly lower in group F than in group C, although few subjects had seroprotective titers against A/H3N2 and B. These results suggest that administration of the formula containing prebiotics and fermented milk products may maintain antibody titers for longer periods through the improvement of intestinal microbiota.

  15. Clinical importance of neutralising antibodies against interferon beta in patients with relapsing-remitting multiple sclerosis

    DEFF Research Database (Denmark)

    Sorensen, Per Soelberg; Ross, Christian; Clemmesen, Katja Maria;

    2003-01-01

    Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies.......Interferon beta is the first-line treatment for relapsing-remitting multiple sclerosis, but the drug can induce neutralising antibodies against itself, which might reduce effectiveness. We aimed to assess the clinical effect of neutralising antibodies....

  16. History and Practice: Antibodies in Infectious Diseases.

    Science.gov (United States)

    Hey, Adam

    2015-04-01

    Antibodies and passive antibody therapy in the treatment of infectious diseases is the story of a treatment concept which dates back more than 120 years, to the 1890s, when the use of serum from immunized animals provided the first effective treatment options against infections with Clostridium tetani and Corynebacterium diphtheriae. However, after the discovery of penicillin by Fleming in 1928, and the subsequent introduction of the much cheaper and safer antibiotics in the 1930s, serum therapy was largely abandoned. However, the broad and general use of antibiotics in human and veterinary medicine has resulted in the development of multi-resistant strains of bacteria with limited to no response to existing treatments and the need for alternative treatment options. The combined specificity and flexibility of antibody-based treatments makes them very valuable tools for designing specific antibody treatments to infectious agents. These attributes have already caused a revolution in new antibody-based treatments in oncology and inflammatory diseases, with many approved products. However, only one monoclonal antibody, palivizumab, for the prevention and treatment of respiratory syncytial virus, is approved for infectious diseases. The high cost of monoclonal antibody therapies, the need for parallel development of diagnostics, and the relatively small markets are major barriers for their development in the presence of cheap antibiotics. It is time to take a new and revised look into the future to find appropriate niches in infectious diseases where new antibody-based treatments or combinations with existing antibiotics, could prove their value and serve as stepping stones for broader acceptance of the potential for and value of these treatments. PMID:26104697

  17. Endothelin A receptor antagonism enhances inhibitory effects of anti-ganglioside GD2 monoclonal antibody on invasiveness and viability of human osteosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Bo Liu

    Full Text Available Endothelin-1 (ET-1/endothelin A receptor (ETAR signaling is important for osteosarcoma (OS progression. Monoclonal antibodies (mAbs targeting ganglioside GD2 reportedly inhibit tumor cell viability independent of the immune system. A recent study suggests that ganglioside GD2 may play an important role in OS progression. In the present study, we for the first time explored the effects of anti-GD2 mAb alone or in combination with ETAR antagonist on OS cell invasiveness and viability. Human OS cell lines Saos-2, MG-63 and SJSA-1 were treated with control IgG (PK136 mAb, 50 µg/mL, anti-GD2 14G2a mAb (50 µg/mL, selective ETAR antagonist BQ123 (5 µM, or 14G2a (50 µg/mL+BQ123 (5 µM. Cells with knockdown of ETAR (ETAR-shRNA with or without 14G2a mAb treatment were also tested. Cells treated with selective phosphatidylinositide 3-kinase (PI3K inhibitor BKM120 (50 µM were used as a positive control. Our results showed that BQ123, ETAR-shRNA and 14G2a mAb individually decreased cell invasion and viability, matrix metalloproteinase-2 (MMP-2 expression and activity, PI3k activity, and phosphorylation at serine 473 (ser473 of Akt in OS cells. 14G2a mAb in combination with BQ123 or ETAR-shRNA showed significantly stronger inhibitory effects compared with each individual treatment. In all three cell lines tested, 14G2a mAb in combination with BQ123 showed the strongest inhibitory effects. In conclusion, we provide the first in vitro evidence that anti-ganglioside GD2 14G2a mAb effectively inhibits cell invasiveness, MMP-2 expression and activity, and cell viability in human OS cells. ETAR antagonist BQ123 significantly enhances the inhibitory effects of 14G2a mAb, likely mainly through inhibiting the PI3K/Akt pathway. This study adds novel insights into OS treatment, which will serve as a solid basis for future in vivo studies on the effects of combined treatment of OS with anti-ganglioside GD2 mAbs and ETAR antagonists.

  18. T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2.

    Science.gov (United States)

    Nicoletti, Roberta; Lopez, Salvatore; Bellone, Stefania; Cocco, Emiliano; Schwab, Carlton L; Black, Jonathan D; Centritto, Floriana; Zhu, Liancheng; Bonazzoli, Elena; Buza, Natalia; Hui, Pei; Mezzanzanica, Delia; Canevari, Silvana; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

    2015-01-01

    Ovarian and uterine carcinosarcoma (CS) are characterized by their aggressive clinical behavior and poor prognosis. We evaluated the efficacy of trastuzumab-emtansine (T-DM1), against primary HER2 positive and HER2 negative CS cell lines in vitro and in vivo. Eight primary CS cell lines were evaluated for HER2 amplification and protein expression by fluorescence in situ hybridization, immunohistochemistry, flow cytometry and qRT-PCR. Sensitivity to T-DM1-induced antibody-dependent-cell-mediated-cytotoxicity (ADCC) was evaluated in 4-h-chromium-release-assays. T-DM1 cytostatic and apoptotic activities were evaluated using flow cytometry based proliferation assays. In vivo activity of T-DM1 was also evaluated. HER2 protein overexpression and gene amplification were detected in 25 % (2/8) of the primary CS cell lines. T-DM1 and T were similarly effective in inducing strong ADCC against CS overexpressing HER2 at 3+ levels. In contrast, T-DM1 was dramatically more effective than T in inhibiting cell proliferation (P < 0.0001) and in inducing G2/M phase cell cycle arrest in the HER2 expressing cell lines (shift of G2/M: mean ± SEM from 14.87 ± 1.23 to 66.57 ± 4.56 %, P < 0.0001). Importantly, T-DM1 was highly active at reducing tumor formation in vivo in CS xenografts overexpressing HER2 (P = 0.0001 and P < 0.0001 compared to T and vehicle respectively) with a significantly longer survival when compared to T and vehicle mice (P = 0.008 and P = 0.0001 respectively). T-DM1 may represent a novel treatment option for the subset of HER2 positive CS patients with disease refractory to chemotherapy. PMID:25398397

  19. Antibodies against AT1 receptors are associated with vascular endothelial and smooth muscle function impairment: protective effects of hydroxysafflor yellow A.

    Directory of Open Access Journals (Sweden)

    Zhu Jin

    Full Text Available Ample evidence has shown that autoantibodies against AT1 receptors (AT1-AA are closely associated with human cardiovascular disease. The aim of this study was to investigate mechanisms underlying AT1-AA-induced vascular structural and functional impairments in the formation of hypertension, and explore ways for preventive treatment. We used synthetic peptide corresponding to the sequence of the second extracellular loop of the AT1 receptor (165-191 to immunize rats and establish an active immunization model. Part of the model received preventive therapy by losartan (20 mg/kg/day and hyroxysafflor yellow A (HSYA (10 mg/kg/day. The result show that systolic blood pressure (SBP and heart rate (HR of immunized rats was significantly higher, and closely correlated with the plasma AT1-Ab titer. The systolic response of thoracic aortic was increased, but diastolic effects were attenuated markedly. Histological observation showed that the thoracic aortic endothelium of the immunized rats became thinner or ruptured, inflammatory cell infiltration, medial smooth muscle cell proliferation and migration, the vascular wall became thicker. There was no significant difference in serum antibody titer between losartan and HSYA groups and the immunized group. The vascular structure and function were reversed, and plasma biochemical parameters were also improved significantly in the two treatment groups. These results suggest that AT1-Ab could induce injury to vascular endothelial cells, and proliferation of smooth muscle cells. These changes were involved in the formation of hypertension. Treatment with AT1 receptor antagonists and anti oxidative therapy could block the pathogenic effect of AT1-Ab on vascular endothelial and smooth muscle cells.

  20. An experimental study on labeling monoclonal antibody 4E5 with 131I and the lethal effects of 131I-4E5 against B cell lymphoma

    International Nuclear Information System (INIS)

    Objective: To label the monoclonal antibody 4E5 with 131I and to evaluate the lethal effects of 131I-4E5 against B cell lymphoma. Methods: 4E5 was radiolabeled with 131I using the Iodogen method at room temperature. The labeling efficiency and radiochemical purity was measured with trichloroacetic acid (TCA) precipitation, and the immune activity and stability of 131I-4E5 was analyzed. The lethal effects of 131I-4E5 and 4E5 against Raji cells were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-dipheny-lte-trazolium bromide (MTT) assay. Analysis of variance and t-test were used for data analysis with SPSS 13.0. Results: The labeling rate of 131I-4E5 was (78.3±2.4)%, and the radiochemical purity was (95.7±1.8)%. Its specific activity and radioactive concentration were 0.58 MBq/μg and 3.90 × 1010 Bq/L, respectively. The radiochemical purity of 131I-4E5 mixed with serum and PBS was over 90% after three days. The maximum specific binding efficiency of 131I-4E5 with Raji cells was (36.06±2.63)%. 131I-4E5 exhibited a dose-dependent cytotoxicity against Raji cells. The lethal effect of the high dose group was significantly stronger than that of the low dose group. When the radioactive concentrations were 1.48 × 1010, 7.40 × 109, 3.70 × 109, 1.85 × 109 and 9.25 × 108 Bq/L, the cell inhibition ratios were (52.98±5.19)%, (46.29±2.80)%, (41.05±4.83)%, (33.68±3.79)% and (17.89±2.78)%, respectively (F=33.882, P<0.001). In the 4E5 group, when concentrations of 4E5 were 20.0, 10.0, 5.0, 2.5 and 1.25 mg/L, the cell inhibition ratios were (32.98±3.99)%,(30.88±3.98)%, (27.14±2.05)%, (20.35±4.38)% and (8.42±1.05)%, respectively. Accordingly,significantly higher growth inhibition rates for Raji cells than 4E5 at all antibody concentrations were tested (t=5.290, 5.489, 4.596, 3.986 and 5.515, all P<0.05). Conclusions: The labeling efficiency and radiochemical purity of 131I-4E5 using Iodogen method is high,and the in vitro stability of 131I-4E5 is optimal. 131I-4E5

  1. Prediction of antibody persistency from antibody titres to natalizumab

    DEFF Research Database (Denmark)

    Jensen, Poul Erik H; Koch-Henriksen, Nils; Sellebjerg, Finn; Sørensen, Per S

    2012-01-01

    In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients.......In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients....

  2. Cysteinylation of a monoclonal antibody leads to its inactivation.

    Science.gov (United States)

    McSherry, Troy; McSherry, Jennifer; Ozaeta, Panfilo; Longenecker, Kenton; Ramsay, Carol; Fishpaugh, Jeffrey; Allen, Steven

    2016-01-01

    Post-translational modifications can have a signification effect on antibody stability. A comprehensive approach is often required to best understand the underlying reasons the modification affects the antibody's potency or aggregation state. Monoclonal antibody 001 displayed significant variation in terms of potency, as defined by surface plasmon resonance testing (Biacore), from lot to lot independent of any observable aggregation or degradation, suggesting that a post-translational modification could be driving this variability. Analysis of different antibody lots using analytical hydrophobic interaction chromatography (HIC) uncovered multiple peaks of varying size. Electrospray ionization mass spectrometry (ESI-MS) indicated that the antibody contained a cysteinylation post-translational modification in complementarity-determining region (CDR) 3 of the antibody light chain. Fractionation of the antibody by HIC followed by ESI-MS and Biacore showed that the different peaks were antibody containing zero, one, or two cysteinylation modifications, and that the modification interferes with the ability of the modified antibody arm to bind antigen. Molecular modeling of the modified region shows that this oxidation of an unpaired cysteine in the antibody CDR would block a potential antigen binding pocket, suggesting an inhibition mechanism. PMID:27050640

  3. The status of rheumatoid factor and anti-cyclic citrullinated peptide antibody are not associated with the effect of anti-TNFα agent treatment in patients with rheumatoid arthritis: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Qianwen Lv

    Full Text Available OBJECTIVES: This meta-analysis was conducted to investigate whether the status of rheumatoid factor (RF and anti-cyclic citrullinated peptide (anti-CCP antibody are associated with the clinical response to anti-tumor necrosis factor (TNF alpha treatment in rheumatoid arthritis (RA. METHODS: A systemic literature review was performed using the MEDLINE, SCOPUS, Cochrane Library, ISI Web of Knowledge, and Clinical Trials Register databases, and Hayden's criteria of quality assessment for prognostic studies were used to evaluate all of the studies. The correlation between the RF and anti-CCP antibody status with the treatment effect of anti-TNFα agents was analyzed separately using the Mantel Haenszel method. A fixed-effects model was used when there was no significant heterogeneity; otherwise, a random-effects model was applied. Publication bias was assessed using Egger's linear regression and a funnel plot. RESULTS: A total of 14 studies involving 5561 RA patients meeting the inclusion criteria were included. The overall analysis showed that the pooled relative risk for the predictive effects of the RF and anti-CCP antibody status on patient response to anti-TNFα agents was 0.98 (95% CI: 0.91-1.05, p=0.54 and 0.88 (95% CI: 0.76-1.03, p=0.11, respectively, with I(2 values of 43% (p=0.05 and 67% (p<0.01, respectively. Subgroup analyses of different anti-TNFα treatments (infliximab vs. etanercept vs. adalimumab vs. golimumab, response criteria (DAS28 vs. ACR20 vs. EULAR response, follow-up period (≥ 6 vs. <6 months, and ethnic group did not reveal a significant association for the status of RF and anti-CCP. CONCLUSIONS: Neither the RF nor anti-CCP antibody status in RA patients is associated with a clinical response to anti-TNFα treatment.

  4. Effect of adding crushed Pimpinella anisum, Nigella sativa seeds and Thymus vulgaris mixture to antibiotics-free rations of vaccinated and non-vaccinated male broilers on growth performance, antibody titer and haematological profile

    OpenAIRE

    Mamoun Z. Athamneh; Safaa S. El-Ghousein; Nafez A. Al-Beitawi

    2010-01-01

    This research explores an experimental study conducted to investigate the effect of crushed Pimpinella anisum (PA), Nigella sativa (NS) seeds and Thymus vulgaris (TV) mixture as a feed additive on growth performance and mortality rate (MR), selected antibodies titer (Ab’s) and blood hematological profile of vaccinated and non-vaccinated Lohman male broiler chicks fed free-antibiotics ration. A total of 400 one-day old chicks were distributed into 16 groups (4 treatment x 4 replicates x ...

  5. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

    self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  6. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.;

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  7. Incidence of radiation-induced Graves' disease in patients treated with radioiodine for thyroid autonomy before and after introduction of a high-sensitivity TSH receptor antibody assay

    International Nuclear Information System (INIS)

    Autoimmune hyperthyroidism may occur several months after radioiodine therapy (RIT) for functional thyroid autonomy. Exacerbation of pre-existing subclinical Graves' disease (GD) has been held responsible for this phenomenon. Determination of TSH receptor antibody using solubilised porcine epithelial cell membranes is insensitive and may have failed to diagnose GD in these patients before RIT. Following the introduction of a more sensitive assay, using the human TSH receptor as an antigen, it has been expected that the incidence of radiation-induced GD after RIT for functional thyroid autonomy will be reduced. In a first group of 1,428 patients treated between November 1993 and March 1997 (group I) we used the porcine TRAb assay to exclude GD, while in a second group comprising 1,408 patients treated between January 2000 and December 2001 (group II), GD was excluded using the human TRAb assay. A matched control group of 231 patients was derived from group II. In group I a total of 15 (1.05%) patients developed obvious or suspected radiation-induced GD, while in group II 17 (1.2%) did so; the interval until development of GD was 8.4 and 8.8 months, respectively, after RIT. Serum anti-thyroid peroxidase levels before RIT were elevated in 36.4% of group I patients and 47.1% of group II patients, but in only 5.6% of the control group. Other non-specific signs of mild immunopathy of the thyroid were seen retrospectively in 73.3%, 64.7% and 16.0% of the patients in these three groups, respectively. In conclusion, the introduction of a high-sensitivity TRAb assay did not reduce the incidence of autoimmune hyperthyroidism occurring late after RIT for functional thyroid autonomy, but mild immunopathy of the thyroid is seen more frequently in these patients and seems to be a predisposing factor in the development of radiation-induced GD. (orig.)

  8. Inhibitory Effects of Anti-VEGF Antibody on the Growth and Angiogenesis of Estrogen-induced Pituitary Prolactinoma in Fischer 344 Rats: Animal Model of VEGF-targeted Therapy for Human Endocrine Tumors

    International Nuclear Information System (INIS)

    Estrogen-induced pituitary prolactin-producing tumors (PRLoma) in F344 rats express a high level of vascular endothelial growth factor (VEGF) associated with marked angiogenesis and angiectasis. To investigate whether tumor development in E2-induced PRLoma is inhibited by anti-VEGF monoclonal antibody (G6-31), we evaluated tumor growth and observed the vascular structures. With simultaneous treatment with G6-31 for the latter three weeks of the 13-week period of E2 stimulation (E2+G6-31 group), the following inhibitory effects on the PRLoma were observed in the E2+G6-31 group as compared with the E2-only group. In the E2+G6-31 group, a tendency to reduction in pituitary weight was observed and significant differences were observed as (1) reductions in the Ki-67-positive anterior cells, (2) increases in TUNEL-positive anterior cells, and (3) repair of the microvessel count by CD34-immunohistochemistry. The characteristic “blood lakes” in PRLomas were improved and replaced by repaired microvascular structures on 3D observation using confocal laser scanning microscope. These inhibitory effects due to anti-VEGF antibody might be related to the autocrine/paracrine action of VEGF on the tumor cells, because VEGF and its receptor are co-expressed on the tumor cells. Thus, our results demonstrate that anti-VEGF antibody exerted inhibitory effects on pituitary tumorigenesis in well-established E2 induced PRLomas

  9. Monoclonal antibodies specific for oncofetal antigen – immature laminin receptor protein: Effects on tumor growth and spread in two murine models

    OpenAIRE

    McClintock, Shannon D.; Warner, Roscoe L.; Ali, Saqib; Chekuri, Apurupa; Dame, Michael K.; Attili, Durga; Knibbs, Randall K; Aslam, Muhammad Nadeem; Sinkule, Joseph; Morgan, Alton Charles; Barsoum, Adel; Smith, Lauren B.; Beer, David G.; Johnson, Kent J.; Varani, James

    2015-01-01

    The oncofetal antigen – immature laminin receptor protein (OFA/iLRP) has been linked to metastatic tumor spread for several years. The present study, in which 2 highly-specific, high-affinity OFA/iLRP-reactive mouse monoclonal antibodies were examined for ability to suppress tumor cell growth and metastatic spread in the A20 B-cell leukemia model and the B16 melanoma model, provides the first direct evidence that targeting OFA/iLRP with exogenous antibodies can have therapeutic benefit. While...

  10. The Effect of Combination Therapy with Rituximab and Intravenous Immunoglobulin on the Progression of Chronic Antibody Mediated Rejection in Renal Transplant Recipients

    Science.gov (United States)

    Yun, Jintak; Khvan, Marina; Park, Cheol Whee; Choi, Yeong Jin; Kim, Yong-Soo; Yang, Chul Woo

    2014-01-01

    The treatment for chronic active antibody-mediated rejection (CAMR) remains controversial. We investigated the efficacy of rituximab (RTX) and intravenous immunoglobulin (IVIg) for CAMR. Eighteen patients with CAMR were treated with RTX (375 mg/m2) and IVIg (0.4 g/kg) for 4 days. The efficacy of RTX/IVIg combination therapy (RIT) was assessed by decline in estimated glomerular filtration rate per month (ΔeGFR) before and after RIT. Patients were divided into responder and nonresponder groups based on decrease and no decrease in ΔeGFR, respectively, and their clinical and histological characteristics were compared. Response rate to RIT was 66.7% (12/18), and overall ΔeGFR decreased significantly to 0.4 ± 1.7 mL·min−1·1.73 m−2 per month 6 months after RIT compared to that observed 6 months before RIT (1.8 ± 1.0, P < 0.05). Clinical and histological features between the 12 responders and the 6 nonresponders were not significantly different, but nonresponders had a significantly higher proteinuria levels at the time of RIT (2.5 ± 2.5 versus 7.0 ± 3.5 protein/creatinine (g/g), P < 0.001). The effect of the RIT on ΔeGFR had dissipated in all patients by 1 year post-RIT. Thus, RIT delayed CAMR progression, and baseline proteinuria level was a prognostic factor for response to RIT. PMID:24741626

  11. Red Blood Cell Antibody Identification

    Science.gov (United States)

    ... limited. Home Visit Global Sites Search Help? RBC Antibody Identification Share this page: Was this page helpful? Also known as: Alloantibody Identification; Antibody ID, RBC; RBC Ab ID Formal name: Red ...

  12. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test ... Normally, there are no antibodies against insulin in your blood. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or ...

  13. The Art of Making Antibodies.

    Science.gov (United States)

    Headon, Denis R.

    1986-01-01

    Provides background information for teachers on the nature and production of antibodies. Points out that the production of monoclonal antibodies blends the malignant with the beneficial to create a medical tool of exciting potential. (JN)

  14. Lupus anticoagulants and antiphospholipid antibodies

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000547.htm Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  15. Immunity to rhabdoviruses in rainbow trout: the antibody response

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lapatra, S.E.

    1999-01-01

    detail so far. Analysis of the specificity of anti-virus trout antibodies has been complicated by a generally insufficient ability of the antibodies to bind the viral proteins in assays such as immunoblotting. However, other assays, specifically designed for detection of fish anti IHNV/VHSV antibodies...... occasional detrimental effect on rainbow trout farming. Research efforts have been focused on understanding the mechanisms involved in protective immunity. Several specific and nonspecific cellular and humoral parameters are believed to be involved, but only the antibody response has been characterised in......, have demonstrated that rainbow trout can produce specific and highly functional antibodies that are able to neutralise virus pathogenicity in vitro as well as in vivo. The apparently more restricted antibody response to IHNV and VHSV antigens in fish compared to mammals could possibly be explained by...

  16. Production of monoclonal antibody with Celline-350 bioreactor

    International Nuclear Information System (INIS)

    Monoclonal antibodies are protein that are highly specific and sensitive in their reaction with specific sites on target molecules that they have become reagents of central importance in the diagnostic and treatment of human diseases. This paper reports the use of CELLine-350 bioreactor to produce continuous supply of serum-free breast cancer monoclonal antibody. Initial volume of 5ml (1.5 x 106 viable cells/ml) is inoculated into the bioreactor and harvesting is done every 5 days to obtain high yield monoclonal antibody. The serum-free supernatant is precipitated with 50% saturated ammonia sulfate and the antibody is purified by protein-G affinity chromatography. The concentration of monoclonal antibody successfully produced by the bioreactor is 0.91mg/ml respectively and it is measured by the Lowry method. This result shows that bioreactor Celline-350 is easy to handle and cost effective for the continuous production of serum free monoclonal antibody. (Author)

  17. Design and manufacture of monoclonal antibodies for radioimmunotherapy

    International Nuclear Information System (INIS)

    Appropriate design and manufacture of monoclonal antibodies is fundamental to their use for radioimmunotherapy. Besides the right selection of antibody specificity and affinity, recombinant antibodies can be designed to simplify manufacture and minimise unwanted side effects. Although many innovative new technologies have been developed in recent years, antibodies are still most commonly produced from mammalian cells and purified by column chromatography. Purification methods have to be designed and validated to remove potential contaminants, especially retroviruses which in principle might be present in mammalian cell lines. Adherence to relevant Good Manufacturing Practice is mandatory in the production of any medicinal product and there are numerous guidelines regarding the manufacture of antibodies. This article outlines some methods used for fermentation, purification and quality control of antibodies intended for radiolabelling

  18. Recombinant antibodies and tumor targeting

    OpenAIRE

    Sheikholvaezin, Ali

    2006-01-01

    Different antibody derived constructs are rapidly advancing as putative tools for treatment of malignant diseases. Antibody engineering has added significant new technologies to modify size, affinities, solubility, stability and biodistribution properties for immunoconjugates. In the present thesis, the aim was to increase our knowledge on how new recombinant antibodies could be tailored to optimize localization to experimental tumors in mice. One hybridoma, producing the monoclonal antibody ...

  19. Antibody Engineering and Therapeutics Conference

    OpenAIRE

    Larrick, James W; Parren, Paul WHI; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A.; Burton, Dennis R.; Adams, Gregory P; Weiner, Louis M.; Scott, Jamie K; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M

    2013-01-01

    The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Bi...

  20. Biophysical characterization of a model antibody drug conjugate.

    Science.gov (United States)

    Arakawa, Tsutomu; Kurosawa, Yasunori; Storms, Michael; Maruyama, Toshiaki; Okumura, C J; Maluf, Nasib Karl

    2016-01-01

    Antibody drug conjugates (ADC) are important next-generation biopharmaceuticals and thus require stringent structure characterization as is the case for monoclonal antibodies. We have tested several biophysical techniques, i.e., circular dichroism, analytical ultracentrifugation, differential scanning calorimetry and fluorescence spectroscopy, to characterize a fluorescein-labeled monoclonal antibody as a model ADC. These techniques indicated possible small structure and stability changes by the conjugation, while largely retaining the tertiary structure of the antibody, consistent with unaltered biological activities. Thus, the above biophysical techniques are effective at detecting changes in the structural properties of ADC. PMID:27534450

  1. Radiolabeled antibodies as imaging agents

    International Nuclear Information System (INIS)

    The author gives a survey of the progress made on radioimmunodetection. Antibodies may now be more readily used in scintigraphy as a result of the development of labeling methods that apply more suitable radionuclides without significant loss of the antigen-binding activity. Antibodies to tumor-specific or tumor-associated antigens can now be produced in large quantities by monoclonal antibody technology

  2. Immunogenicity of anti-tumor necrosis factor antibodies-toward improved methods of anti-antibody measurement.

    Science.gov (United States)

    Aarden, Lucien; Ruuls, Sigrid R; Wolbink, Gertjan

    2008-08-01

    To date, millions of people have been treated with therapeutic monoclonal antibodies (TmAbs) for various indications. It is becoming increasingly clear that TmAbs can be immunogenic, which may reduce efficacy or induce adverse effects. Over the years, the importance of antibody formation has been questioned and sometimes minimized, as few antibody responses to TmAbs (HACA or HAHA) were reported. However, the methods to detect and quantify such antibodies used in the past have been problematic. Only recently, methods have been developed that have adequate sensitivity and are not seriously disturbed by false-positive reactions caused by rheumatoid factors, natural antibodies to Fab or F(ab')2 fragments, or Fc interactions of IgG4. The large number of treated patients, in combination with these new assays, presents a unique opportunity to study the anti-antibody immune response in man, possibly allowing us to manipulate immunogenicity in the future. PMID:18619538

  3. Stability of rhenium-188 labeled antibody

    International Nuclear Information System (INIS)

    For clinical application of beta-emitter labeled antibody, high specific activity is important. Carrier-free Re-188 from W-188/Re-188 generator is an ideal radionuclide for this purpose. However, low stability of Re-188 labeled antibody, especially in high specific activity, due to radiolytic decomposition by high energy (2.1 MeV) beta ray was problem. We studied the stability of Re-188 labeled antibody, and stabilizing effect of several nontoxic radical-quenching agents. Pre-reduced monoclonal antibody (CEA79.4) was labeled with Re-188 by incubating with generator-eluted Re-188-perrhenate in the presence of stannous tartrate for 2 hr at room temperature. Radiochemical purity of each preparation was determined by chromatography (ITLC-SG/acetone, ITLC-SG/Umezawa, Whatman No.1/saline). Human serum albumin was added to the labeled antibodies(2%). Stability of Re-188-CEA79.4 was investigated in the presence of vitamin C, ethanol, or Tween 80 as radical-quenching agents. Specific activities of 4.29∼5.11 MBq/μg were obtained. Labeling efficiencies were 88±4%(n=12). Very low stability after removal of stannous tartrate from the preparation was observed. If stored after purging with N2, all the preparations were stable for 10 hr. However, if contacted with air, stability decreased. Perrhenate and Re-188-tartrate was major impurity in declined preparation (12∼47 and 9∼38% each, after 10 hr). Colloid-formation was not a significant problem in all cases. Addition of vitamin C stabilized the labeled antibodies either under N2 or under air by reducing the formation of perrhenate. High specific activity Re-188 labeled antibody is unstable, especially, in the presence of oxygen. Addition of vitamin C increased the stability

  4. Preparation of studies on antibody production against food allergens in mice and effect of flavonoids in simultaneous injection into mouse skin.

    Science.gov (United States)

    We had tried to evaluate antibody production against food allergens in mouse models. Some food allergens, which were beta-lactoglobulin, ovalbumin, and peanut allergen Ara h 1, were used as immunoges in this experiment. Under the same conditions these allergens were immunized as emulsion with freund...

  5. Antibody mimetics: promising complementary agents to animal-sourced antibodies.

    Science.gov (United States)

    Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying

    2016-01-01

    Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed. PMID:25264572

  6. Properties of a general PK/PD model of antibody-ligand interactions for therapeutic antibodies that bind to soluble endogenous targets

    OpenAIRE

    Davda, Jasmine P; Hansen, Ryan J.

    2010-01-01

    Antibodies that target endogenous soluble ligands are an important class of biotherapeutic agents. While much focus has been placed on characterization of antibody pharmacokinetics, less emphasis has been given to characterization of antibody effects on their soluble targets. We describe here the properties of a generalized mechanism-based PK/PD model used to characterize the in vivo interaction of an antibody and an endogenous soluble ligand. The assumptions and properties of the model are e...

  7. N-Propionyl polysialic acid precursor enhances the susceptibility of multiple myeloma to antitumor effect of anti-NprPSA monoclonal antibody

    Institute of Scientific and Technical Information of China (English)

    Hong XIONG; Ai-bin LIANG; Bing XIU; Jian-fei FU; Yi DING; Yu-hua CHEN

    2012-01-01

    Aim: To study the antitumor effect of anti-NprPSA monoclonal antibody (mAb) in combination with ManNPr,a precursor of N-propionyl PSA,in multiple myeloma (MM),and to explore the mechanisms of the action.Methods: Human multiple myeloma cell line RPMI-8226 was tested.The cells were pre-treated with ManNPr (1,2,and 4 mg/mL),and then incubated with anti-NprPSA mAb (1 mg/mL).Cell apoptosis in vitro was detected using MTT assay and flow cytometry.BALB/c nude mice were inoculated sc with RPC5.4 cells.On 5 d after the injection,the mice were administered sc with anti-NprPSA mAb (200 μg/d) and ManNPr (5 mg/d) for 8 d.The tumor size and body weight were monitored twice per week.TUNEL assay was used for detecting apoptosis in vivo.The apoptotic pathway involved was examined using Western blot analysis and caspase inhibitor.Results: Treatment of RPMI-8226 cells with anti-NprPSA mAb alone failed to inhibit cell growth in vitro.In RPM1-8226 ceils pretreated with ManNPr,however,the mAb significantly inhibited the cell proliferation,decreased the viability,and induced apoptosis,which was associated with cleavage of caspase-3,caspase-8,caspase-9,and poly(ADP-ribose) polymerase.In the mouse xenograft model,treatment with the mAb in combination with ManNPr significantly inhibited the tumor growth,and induced significant apoptosis as compared to treatment with the mAb alone.Moreover,apoptosis induced by the mAb in vivo resulted from the activation of the caspases and poly(ADP-ribose) polymerase.Conclusion: The anti-NprPSA mAb in combination with ManNPr is an effective treatment for in vitro and in vivo induction of apoptosis in multiple myeloma.

  8. Perfluorooctanoic Acid Exposure Suppresses T-independent Antibody Responses

    Science.gov (United States)

    Exposure to  3.75mg/kg of perfluoroocatnoic acid (PFOA) for 15d suppresses T-dependent antibody responses (TDAR), suggesting that T helper cells and/or B cells/plasma cells may be impacted. This study evaluated effects of PFOA exposure on the T cell-independent antibody response...

  9. In vivo modulators of antibody kinetics

    International Nuclear Information System (INIS)

    The aim of the present study was to summarize the effect of in vivo modulation of antibody kinetics and to present new data on the in vivo effect of the cell membrane active detergent Tween 80 and the cytokine interleukin-2 (IL-2) on the accumulation and clearance of a radioactive antibody. Mice bearing Lewis lung carcinoma xenografts and rats bearing DMBA-induced mammary carcinomas were studied after injecting I-125 labeled IgG1 monoclonal antibody (3c4c7g6) raised against a tyrosine kinase receptor protein Tie. Expression of Tie is known to be abundant in vascular endothelia and possibly related to malignant angiogenesis. Tween 80 was administered intratumorally (0.04% of tumor volume), whereas IL-2 was administered intraperitoneally. In the Lewis lung tumor model, the absolute tumor uptake varied between 2 and 5% ID/g, and maximum uptake was achieved after 24 h with Tween, and after 48 h without Tween. Tween manipulation did not increase the uptake in any normal organ, but it enhanced antibody clearance form the blood. In the DMBA rat model, IL-2 had no effect on blood clearance, but enhanced the uptake of Tie antibody into the tumor from 2.5-0.9 to 4.5-0.4% ID/g at 48 h. These data indicate that antibody biodistribution and pharmacokinetics can be modulated by a surface detergent and a cytokine, giving decreased exposure to critical organs, and increased uptake into the tumor. This type of manipulation provides an opportunity to optimize radioimmunotherapy. (orig.)

  10. Monoclonal antibodies to Pneumocystis carinii

    DEFF Research Database (Denmark)

    Kovacs, J A; Halpern, J L; Lundgren, B; Swan, J C; Parrillo, J E; Masur, H

    1989-01-01

    To increase understanding of the antigenic structure of Pneumocystis carinii, we developed monoclonal antibodies to rat and human P. carinii. The specificity of the antibodies was demonstrated by immunofluorescence and immunoblot studies. Only one of five monoclonal antibodies to rat P. carinii...... reacted with human P. carinii, and none of four monoclonal antibodies to human P. carinii reacted with rat P. carinii. Two antibodies to human P. carinii reacted by immunofluorescence with only one human P. carinii isolate. Immunoblot studies identified major antigens of rat P. carinii with molecular...

  11. Tabhu: tools for antibody humanization

    DEFF Research Database (Denmark)

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna

    2015-01-01

    and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps......Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can...

  12. Separation of hemagglutination-inhibiting immunoglobulin M antibody to rubella virus in human serum by high-performance liquid chromatography.

    OpenAIRE

    N. Kobayashi; M. Suzuki; Nakagawa, T.; Matumoto, M

    1986-01-01

    High-performance liquid chromatography was successfully used to separate hemagglutination-inhibiting immunoglobulin M (IgM) rubella virus antibody from IgG rubella virus antibody in human serum. The fractionation by high-performance liquid chromatography was as effective as sucrose density gradient centrifugation in separating IgM antibody from IgG antibody.

  13. Monoclonal antibody as radiopharmaceutical

    International Nuclear Information System (INIS)

    The purification of anti-CEA monoclonal antibody 4C11 belonging to IgG sub(2a) subclass from mouse ascitis, donated by Ludwig Institute, Brazil was developed. The fragmentation of purified IgG sub(2a) by pepsin digestion and analytical studies by polyacrilamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE) were done as preliminary assessment for their specific application in immunoscintigraphy. (author)

  14. Anticardiolipin antibodies in leptospirosis.

    OpenAIRE

    Rugman, F P; Pinn, G.; Palmer, M. F.; Waite, M.; Hay, C. R.

    1991-01-01

    The clinical course and serology of 16 cases of leptospirosis in an area with an unusually high endemic infection rate were studied to gain further insight into the pathology of the secondary immune phase that is typical of the disease. IgG anticardiolipin antibody concentrations were measured by immunoassay and found to be increased in eight serologically confirmed cases with severe complicated disease, compared with eight patients with relatively uncomplicated leptospirosis who had IgG anti...

  15. A monoclonal antibody against leptin.

    Science.gov (United States)

    Mahmoudian, Jafar; Jeddi-Tehrani, Mahmood; Bayat, Ali Ahmad; Mahmoudi, Ahmad Reza; Vojgani, Yasaman; Tavangar, Banafsheh; Hadavi, Reza; Zarei, Saeed

    2012-10-01

    Leptin is an important protein that regulates energy storage and homeostasis in humans and animals. Leptin deficiency results in various abnormalities such as diabetes, obesity, and infertility. Producing a high affinity monoclonal antibody against human leptin provides an important tool to monitor and trace leptin function in different biological fluids. In this study, recombinant human leptin was conjugated to KLH and injected into mice. After immunization, mouse myeloma SP2/0 cells were fused with murine splenocytes followed by selection of antibody-producing hybridoma cells. After screening of different hybridoma colonies by ELISA, a high affinity antibody was selected and purified by affinity chromatography. The affinity constant of the antibody was measured by ELISA. Western blot, immunocytochemistry, and flow cytometry experiments were used to characterize the antibody. The anti-leptin antibody had a high affinity (around 1.13 × 10(-9) M) for its antigen. The saturation of the antibody with leptin (20 moles leptin per 1 mole antibody) in Western blot analysis proved that the antibody had specific binding to its antigen. Immunocytochemistry and flow cytometry on JEG-3 (human placental choriocarcinoma cell) cells revealed that the anti-leptin antibody recognized intracellular leptin. In conclusion, we report here the production and characterization of a murine anti-leptin antibody with high affinity for human leptin. PMID:23098305

  16. Analysis of defined combinations of monoclonal antibodies in anthrax toxin neutralization assays and their synergistic action.

    Science.gov (United States)

    Ngundi, Miriam M; Meade, Bruce D; Little, Stephen F; Quinn, Conrad P; Corbett, Cindi R; Brady, Rebecca A; Burns, Drusilla L

    2012-05-01

    Antibodies against the protective antigen (PA) component of anthrax toxin play an important role in protection against disease caused by Bacillus anthracis. In this study, we examined defined combinations of PA-specific monoclonal antibodies for their ability to neutralize anthrax toxin in cell culture assays. We observed additive, synergistic, and antagonistic effects of the antibodies depending on the specific antibody combination examined and the specific assay used. Synergistic toxin-neutralizing antibody interactions were examined in more detail. We found that one mechanism that can lead to antibody synergy is the bridging of PA monomers by one antibody, with resultant bivalent binding of the second antibody. These results may aid in optimal design of new vaccines and antibody therapies against anthrax. PMID:22441391

  17. Acute effects of radioiodine therapy on the voice and larynx of basedow-Graves patients

    International Nuclear Information System (INIS)

    Graves's disease is the most common cause of hyperthyroidism. There are three current therapeutic options: anti-thyroid medication, surgery, and radioactive iodine (I 131). There are few data in the literature regarding the effects of radioiodine therapy on the larynx and voice. The aim of this study was: to assess the effect of radioiodine therapy on the voice of Basedow-Graves patients. Material and method: A prospective study was done. Following the diagnosis of Grave's disease, patients underwent investigation of their voice, measurement of maximum phonatory time (/a/) and the s/z ratio, fundamental frequency analysis (Praat software), laryngoscopy and (perceptive-auditory) analysis in three different conditions: pre-treatment, 4 days, and 20 days post-radioiodine therapy. Conditions are based on the inflammatory pattern of thyroid tissue (Jones et al. 1999). Results: No statistically significant differences were found in voice characteristics in these three conditions. Conclusion: Radioiodine therapy does not affect voice quality. (author)

  18. Antiphospholipid Antibody and Antiphospholipid Syndrome

    Institute of Scientific and Technical Information of China (English)

    吴竞生

    2008-01-01

    @@ Antiphospholipid antibodies (APA) APA is a big category for all kinds of negative charge phospholipid or lecithin - a protein complex autoantibodies or the same antibody, through its recognition of antigen (target protein) different, and phospholipids or lecithin - protein complex combination of various rely on the interference Phospholipid clotting and anti-coagulation factor, and promote endothelial cells, platelets, complement activation and play a role. APA including lupus anticoagulant(LA) and anticardiolipin antibody (ACA), In addition, there are anti-β2 glycoprotein-I (β2-GPI) antibody, anti-prothrombin (a- PT) antibody, anti-lysophosphatidic acid antibody and anti-phosphatidylserine antibody, and so on. APA as the main target of phospholipid-binding protein, including β2-GPI, prothrombin, annexin, protein C (PC) and protein S (PS), plasminogen, and so on.

  19. Cell-targeting antibodies in immunity to Ebola.

    Science.gov (United States)

    Schmaljohn, Alan; Lewis, George K

    2016-06-01

    As the 2014-15 Ebola virus epidemic in West Africa evolved from emergency to lesson, developers of both vaccines and therapeutic antibodies were left with the puzzlement of what kinds of anti-Ebola antibodies are predictably desirable in treating the afflicted, and what antibodies might account for the specific and lasting protection elicited by the more effective vaccines. The facile answer in virology is that neutralizing antibody (NAb) is desired and required. However, with Ebola and other filoviruses (as with many prior viral examples), there are multiple discordances in which neutralizing antibodies fail to protect animals, and others in which antibody-mediated protection is observed in the absence of measured virus neutralization. Explanation presumably resides in the protective role of antibodies that bind and functionally 'target' virus-infected cells, here called 'cell-targeting antibody', or CTAb. To be clear, many NAbs are also CTAbs, and in the case of Ebola the great majority of NAbs are likely CTAbs. Isotype, glycosylation, and other features of CTAbs are likely crucial in their capacity to mediate protection. Overall, results and analysis invite an increasingly complex view of antibody-mediated immunity to enveloped viruses. PMID:27005312

  20. Pre-existing Antibody: Biotherapeutic Modality-Based Review.

    Science.gov (United States)

    Gorovits, Boris; Clements-Egan, Adrienne; Birchler, Mary; Liang, Meina; Myler, Heather; Peng, Kun; Purushothama, Shobha; Rajadhyaksha, Manoj; Salazar-Fontana, Laura; Sung, Crystal; Xue, Li

    2016-03-01

    Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naïve subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodies vary from an adverse effect on patient safety to no impact at all and remain highly dependent on the biotherapeutic drug modality and therapeutic indication. As such, pre-existing antibodies are viewed as an immunogenicity risk factor requiring a careful evaluation. Herein, the relationships between biotherapeutic modalities to the nature, prevalence, and clinical consequences of pre-existing antibodies are reviewed. Initial evidence for pre-existing antibody is often identified during anti-drug antibody (ADA) assay development. Other interfering factors known to cause false ADA positive signal, including circulating multimeric drug target, rheumatoid factors, and heterophilic antibodies, are discussed. PMID:26821802

  1. 规模猪场不同免疫次数对口蹄疫抗体产生效果的影响%Effects of different immunization times on FMDV antibodies from pigs in intensive pig farms

    Institute of Scientific and Technical Information of China (English)

    韦显凯; 郑敏; 郑列丰; 苏姣秀; 颜健华; 梁晟; 钟一治; 何贻坚; 李军

    2014-01-01

    【目的】探讨规模猪场不同免疫次数对口蹄疫病毒(FMDV)抗体产生的影响,为指导口蹄疫(FMD)免疫提供理论依据。【方法】以存栏母猪100头为分界,从广西16家不同规模养猪场采集经FMD疫苗一免、二免和三免后1个月的血清,共720份,然后使用ELISA试剂盒对血清样品的FMDV抗体水平进行检测。【结果】两种规模猪场猪群一免、二免和三免后1个月产生的FMDV抗体总合格率分别为52.08%、72.08%和86.67%,对应平均抗体离散度分别为53.83%、75.75%和106.46%,S/N值分别为0.527、0.387和0.294。其中,一免和三免的FMDV抗体合格率、S/N值差异极显著(P0.05)。【结论】FMD免疫一次远达不到国家要求的免疫效果,经过三免后FMD免疫效果最佳。实际生产中,规模化猪场应加强对猪群FMDV抗体的监测,并根据抗体消长规律有针对性地进行免疫,提高猪群抗体水平的均匀度,有效防控FMD流行。%[Objective]Effects of different immunization times on FMDV antibodies from pigs in intensive pig farms were studied to provide references for FMDV immunization. [Method]Taking 100 sows as a boundary, 720 pig serum samples were collected from 16 farms. These serum samples had been collected after one month of prime, first boost and second boost for FMD vaccination, respectively. The antibody levels of these serum samples were measured by blocking-ELISA technique.[Result]The ratio of antibody positive of prime, first boost and second boost for FMD was 52.08%,72.08%and 86.67%, and dispersion was 53.83%,75.75%and 106.46%. S/N level was 0.527, 0.387 and 0.294, respectively. The ratio of antibody positive of prime and second boost and S/N level were extremely significantly different (P0.05). [Conclusion]The prime immunization could not meet national standards. The second boost immunization showed the best antibody levels. In practical operation, intensive pig farms should enhance

  2. Systemic CD8+ T cell-mediated tumoricidal effects by intratumoral treatment of oncolytic herpes simplex virus with the agonistic monoclonal antibody for murine glucocorticoid-induced tumor necrosis factor receptor.

    Directory of Open Access Journals (Sweden)

    Mikiya Ishihara

    Full Text Available Oncolytic virotherapy combined with immunomodulators is a novel noninvasive strategy for cancer treatment. In this study, we examined the tumoricidal effects of oncolytic HF10, a naturally occurring mutant of herpes simplex virus type-1, combined with an agonistic DTA-1 monoclonal antibody specific for the glucocorticoid-induced tumor necrosis factor receptor. Two murine tumor models were used to evaluate the therapeutic efficacies of HF10 virotherapy combined with DTA-1. The kinetics and immunological mechanisms of DTA-1 in HF10 infection were examined using flow cytometry and immunohistochemistry. Intratumoral administration of HF10 in combination with DTA-1 at a low dose resulted in a more vigorous attenuation of growth of the untreated contralateral as well as the treated tumors than treatment with either HF10 or DTA-1 alone. An accumulation of CD8(+ T cells, including tumor- and herpes simplex virus type-1-specific populations, and a decrease in the number of CD4(+ Foxp3(+ T regulatory cells were seen in both HF10- and DTA-1-treated tumors. Studies using Fc-digested DTA-1 and Fcγ receptor knockout mice demonstrated the direct participation of DTA-1 in regulatory T cell depletion by antibody-dependent cellular cytotoxicity primarily via macrophages. These results indicated the potential therapeutic efficacy of a glucocorticoid-induced tumor necrosis factor receptor-specific monoclonal antibody in oncolytic virotherapy at local tumor sites.

  3. Effect of ingested human antibodies induced by RTS, S/AS01 malaria vaccination in children on Plasmodium falciparum oocyst formation and sporogony in mosquitoes

    DEFF Research Database (Denmark)

    Miura, Kazutoyo; Jongert, Erik; Deng, Bingbing;

    2014-01-01

    BACKGROUND: The circumsporozoite protein (CS protein) on the malaria parasites in mosquitoes plays an important role in sporogony in mosquitoes. The RTS,S/AS01 malaria vaccine candidate, which has shown significant efficacy against clinical malaria in a large Phase 3 trial, targets the Plasmodium...... falciparum CS protein, but the ability of serum from vaccinated individuals to inhibit sporogony in mosquitoes has not been evaluated. METHODS: Previously a double-blind, randomized trial of RTS,S/AS01 vaccine, as compared with rabies vaccine, in five- to 17-month old children in Tanzania was conducted. In...... antibodies to inhibit P. falciparum oocyst formation and/or sporogony in the mosquito host was evaluated by a standard membrane-feeding assay. The test antibodies were fed on day 0 (at the same time as the gametocyte feed), or on days 3 or 6 (serial-feed experiments). The oocyst and sporozoite counts were...

  4. Vaccination of Rhesus Macaques with the Anthrax Vaccine Adsorbed Vaccine Produces a Serum Antibody Response That Effectively Neutralizes Receptor-Bound Protective Antigen In Vitro ▿

    OpenAIRE

    Clement, Kristin H.; Rudge, Thomas L.; Mayfield, Heather J.; Carlton, Lena A.; Hester, Arelis; Niemuth, Nancy A.; Sabourin, Carol L.; Brys, April M.; Quinn, Conrad P.

    2010-01-01

    Anthrax toxin (ATx) is composed of the binary exotoxins lethal toxin (LTx) and edema toxin (ETx). They have separate effector proteins (edema factor and lethal factor) but have the same binding protein, protective antigen (PA). PA is the primary immunogen in the current licensed vaccine anthrax vaccine adsorbed (AVA [BioThrax]). AVA confers protective immunity by stimulating production of ATx-neutralizing antibodies, which could block the intoxication process at several steps (binding of PA t...

  5. Anti-cocaine antibody and butyrylcholinesterase-derived cocaine hydrolase exert cooperative effects on cocaine pharmacokinetics and cocaine-induced locomotor activity in mice

    OpenAIRE

    Brimijoin, Stephen; Orson, Frank; Kosten, Tom; Kinsey, Berma; Shen, Xiao Yun; White, Sarah J.; Gao, Yang

    2012-01-01

    We are investigating treatments for cocaine abuse based on viral gene transfer of a cocaine hydrolase (CocH) derived from human butyrylcholinesterase, which can reduce cocaine-stimulated locomotion and cocaine-primed reinstatement of drug-seeking behavior in rats for many months. Here, in mice, we explored the possibility that anti-cocaine antibodies can complement the actions of CocH to reduce cocaine uptake in brain and block centrally-evoked locomotor stimulation. Direct injections of test...

  6. Effects of experimental immunosuppression in cattle with persistently high antibody levels to Salmonella Dublin lipopolysaccharide O-antigens

    OpenAIRE

    Nielsen Liza R; Jensen Asger L; Agerholm Jørgen S; Lomborg Sanne R

    2007-01-01

    Abstract Background Salmonella Dublin (S. Dublin) is a zoonotic bacterium which is host adapted to cattle. The bacterium can cause subclinical persistent infection in cattle (carriers), which may be reactivated. During reactivation, animals may shed bacteria, thus constituting a source of infection for other animals. Identification of such carriers is assumed to be critical in attempts to control and eradicate the infection. Some authors suggest that persistently high antibody levels in serum...

  7. Pneumococcal Surface Protein A Is Expressed In Vivo, and Antibodies to PspA Are Effective for Therapy in a Murine Model of Pneumococcal Sepsis

    OpenAIRE

    Swiatlo, E.; J. King; Nabors, G S; Mathews, B; Briles, D. E.

    2003-01-01

    Pneumococcal surface protein A (PspA) is an immunogenic protein expressed on the surface of all strains of Streptococcus pneumoniae (pneumococcus) and induces antibodies which protect against invasive infection in mice. Pneumococci used for infectious challenge in protection studies are typically collected from cultures grown in semisynthetic medium in vitro. The purpose of these studies is to confirm that PspA is expressed by pneumococci during growth in vivo at ...

  8. EFFECT OF VL AND VH CONSENSUS SEQUENCE-SPECIFIC PRIMERS ON THE BINDING AND EXPRESSION OF A MINI- MOLECULE ANTIBODY DIRECTED TOWARDS HUMAN GASTRIC CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective. To construct ScFv and Fab from murine anti-gastric cancer monoclonal antibody( mAb)3H11. Methods. At first,3H11 ScFv and Fab were constructed with V genes PCR amplified by degenerate primers for FRI. The bacterial expressed 3H11 Ab fragments showed no antigen binding activity. Then, phage antibody library andrandom mutated library were constructed from 3H1 1 hybridoma cells and panning selection was performed. Again the i-dentification of positive clone was failed. Finally the N-terminal sequences of V regions were resumed to 3H1 1 original sequences by site-directed mutagenesis via PCR. Results. Binding activity to gastric cancer cells was detected only from N-terminal sequence corrected 3H11 ScFv and Fab,though the expression of the Ab fiagments was not affected. Correction of either VL or VH N-terminal se-quences could partially resume the antigen binding activity. Conclusion. Sequence changes of V region N terminal introduced by PCR may seriously affect antigen binding without affecting the expression of antibody. Received for publication Oct. 26,1998.

  9. Second antibody clearance of radiolabeled antibody in cancer radioimmunodetection.

    OpenAIRE

    Sharkey, R M; Primus, F J; Goldenberg, D. M.

    1984-01-01

    The imaging of tumors using radiolabeled antibodies previously has required the implementation of computer-assisted subtraction techniques to reduce background radioactivity. A decrease in radioactivity in the blood of hamsters bearing human colonic tumor xenografts has been achieved by administering a second antibody directed against a radiolabeled primary antibody to carcinoembryonic antigen (CEA). This method was found to reduce the level of blood radioactivity by a factor of 4 within 2 hr...

  10. Effect of chelator conjugation level and injection dose on tumor and organ uptake of 111In-labeled MORAb-009, an anti-mesothelin antibody

    International Nuclear Information System (INIS)

    Introduction: Radiolabeling of a monoclonal antibody (mAb) with a metallic radionuclide requires the conjugation of a bifunctional chelator to the mAb. The conjugation, however, can alter the physical and immunological properties of the mAb, consequently affecting its tumor-targeting pharmacokinetics. In this study, we investigated the effect of the amount of 2-(p-isothiocyanatobenzyl)-cyclohexyl-diethylenetriamine-pentaacetic acid (CHX-A″) conjugated to MORAb-009, a mAb directed against mesothelin, and the effect of MORAb dose on the biodistribution of 111In-labeled MORAb-009. Methods: We used nude mice bearing the A431/K5 tumor as a mesothelin-positive tumor model and the A431 tumor as a mesothelin-negative control. To find the optimal level of CHX-A″ conjugation, CHX-A″-MORAb-009 conjugates with 2.4, 3.5 and 5.5 CHX-A″ molecules were investigated. To investigate the effect of injected MORAb-009 dose on neutralizing the shed mesothelin in the circulation, biodistribution studies were performed after the intravenous co-injection of 111In-labeled MORAb-009 (2.4 CHX-A″/MORAb-009) with three different doses: 0.2, 2 and 30 μg of MORAb-009. Results: The tumor uptake in A431/K5 tumor was four times higher than that in A431 tumor, indicating that the tumor uptake in A431/K5 was mesothelin mediated. The conjugate with 5.5 CHX-A″ showed a lower isoelectric point (pI) and lower immunoreactivity (IR) than the 2.4 CHX-A″ conjugate. These differences were reflected in the biodistribution of the 111In label. The 111In-labeled MORAb-009 conjugated with 2.4 CHX-A″ produced higher tumor uptake and lower liver and spleen uptakes than the 5.5 CHX-A″ conjugate. The biodistribution studies also revealed that the tumor uptake was significantly affected by the injected MORAb-009 dose and tumor size. The 30-μg dose produced higher tumor uptake than the 0.2- and 2-μg doses, whereas the 30-μg dose produced lower liver and spleen uptakes than the 0.2-μg dose

  11. Autoimmune polyglandular syndrome type 3 complicated by mineralocorticoid-responsive hyponatremia of the elderly

    Directory of Open Access Journals (Sweden)

    Hidekatsu Yanai

    2010-09-01

    Full Text Available We experienced the first case with autoimmune polyglandular syndrome type 3 (anti-thyroid peroxidase antibody-positive hypothyroidism and anti-glutamic acid decarboxylase antibody-positive diabetes complicated by mineralocorticoid-responsive hyponatremia of the elderly. This case is also a rare slowly progressive insulin-dependent diabetes mellitus (SPIDDM case, for which the patient has been treated for many years with sulfonylurea or glinide. Our observation also demonstrated that glucose metabolism in autoimmune diabetes such as SPIDDM is influenced by appetite, thyroid function and glucocorticoid effect.

  12. Antibody Glossary —

    Science.gov (United States)

    The components of the immune system have diverse roles in the initial development of cancers, progression of early-stage malignancies to invasive tumors, establishment of metastatic lesions, tumor dormancy, and response or resistance to therapy. Characterizing the components of the immune system and their functional status in tissues and in tumors requires the use of highly specific reagents. Researchers employ antibodies in a variety of in vitro and in vivo applications to delineate, enrich, or deplete specific immune subsets in order to understand their role(s) in tumorigenesis. This is a glossary of validated reagents and protocols that are useful for functional phenotyping of the immune system in murine cancer models.

  13. The antibody Hijikata Tatsumi

    Directory of Open Access Journals (Sweden)

    Éden Peretta

    2012-11-01

    Full Text Available Considered one of the most influential modern dance representatives in Japan, Tatsumi Hijikata’s work was a milestone in the Japanese post-war experimental artistic scene. Heretic son of his time, he staged a fertile mix of artistic and cultural influences, overlapping subversive elements of European arts and philosophy with radical references from pre-modern Japanese culture. In this way he built the foundations of its unstable antibody, its political-artistic project of dissolution of a organism, both physical and social.

  14. Neutralization of lymphokine-mediated antirickettsial activity of fibroblasts and macrophages with monoclonal antibody specific for murine interferon gamma.

    OpenAIRE

    Jerrells, T R; Turco, J; Winkler, H H; Spitalny, G L

    1986-01-01

    Lymphokine-mediated inhibition of Rickettsia prowazekii multiplication in L929 fibroblasts was eliminated by treatment of the lymphokine with a monoclonal antibody specific for interferon-gamma. Soluble monoclonal antibody and antibody conjugated to Sepharose beads were equally effective. Macrophage activation to limit the multiplication of Rickettsia conorii was eliminated with antibody-conjugated beads; however, neutralization of the ability to activate macrophages with soluble antibody was...

  15. VIRAL ANTIBODIES IN PRESCHOOL CHILDREN

    Directory of Open Access Journals (Sweden)

    S. Saidi

    1974-08-01

    Full Text Available One hundred sera from children 1 - 6 years of age, representative of a large serum collection, were tested for the prevalence of antibodies against different viruses. Hemagglutination-inhibition (HI antibodies were found in 68% for measles; 61 % for rubella; 75'% for influenza A2/Hong Kong/68, 16% for influenza B/Md./59, 0% for group A arboviruses, 10% for group B arboviruses, 3% for phlebotomus fever group and 4% for Congo-Crimean hemorrhagic fever (C-CHF group of arboviruses Poliomyelitis-neutralizing antibodies for type 1, 2 and 3 were 90%; 85% and 84%~ respectively. Antibody to EH virus was detected in 84% of the sera by immuno-fluorescence. None of the sera were positive for hepatitis-B antigen or antibody by immuno-precipitation test. The prevalence of some viral antibodies found in this survey are compared with results obtained from surveys in other parts of the country.

  16. Suppression of contractile force in muscle fibers by antibody to myosin subfragment 2.

    OpenAIRE

    Lovell, S; Karr, T; Harrington, W F

    1988-01-01

    Polyclonal antibody directed against the subfragment-2 region of myosin was purified by affinity chromatography. Skinned muscle fibers that had been preincubated with antibody were able to sustain only 7% of the active isometric force generated by control fibers. The effect of antibody on force production could not be accounted for by inhibition of ATP turnover.

  17. Irregular Antibody Screening Preventive Effect in Hemolytic Transfusion Reaction%不规则抗体筛查在溶血性输血反应中的预防效果

    Institute of Scientific and Technical Information of China (English)

    蔡莉莉

    2016-01-01

    Objective Irregular antibody screening preventive effect was observed in hemolytic transfusion reactions.Methods A retrospective analysis of November 2013 to November 2014 in our hospital 987 cases of elective surgery patients need blood transfusion clinical data to detect patients with micro-gel anti-human globulin serum irregular antibodies, the result is positive specimens for further identification, irregular antibody screening results to be analyzed.Results 987 cases of blood transfusion patients irregular antibody screening found six patients (4 males, 2 females) appeared antibody positive with probability of 0.60%, six cases of patients with irregular antibody in 2 cases of anti-E, 3 cases of anti-cE, 1 cases of anti-D, 2 patients did not last transfusion, the blood center blood transfusion with patients, 4 patients, transfusion reactions did not occur.Conclusion Irregular antibody screening for hemolytic transfusion reaction preventive effect is good, you can ensure safety of blood transfusion patients, improve the efficacy of blood transfusions for the prevention and treatment of neonatal hemolytic disease also has a positive meaning.%目的:观察不规则抗体筛查在溶血性输血反应中的预防效果。方法回顾性分析2013年11月至2014年11月在本院行择期手术987例需输血患者临床资料,使用微柱凝胶抗人球蛋白法检测患者血清不规则抗体,结果为阳性的标本进行进一步鉴定,不规则抗体筛查结果予以分析。结果对987例需输血患者进行不规则抗体筛查发现有6例患者(4例男性,2例女性)出现抗体阳性,阳性概率为0.60%,6例不规则抗体患者中有2例抗-E、3例抗-cE、1例抗-D,最后有2例患者未输血,经血液中心配合血液输血患者有4例,均没有发生输血反应。结论不规则抗体筛查对溶血性输血反应中的预防效果良好,可以确保患者输血安全,提高输血的疗效,对相关溶血病的

  18. Antibodies to watch in 2015

    OpenAIRE

    Reichert, Janice M

    2014-01-01

    The commercial pipeline of recombinant antibody therapeutics is robust and dynamic. As of early December 2014, a total of 6 such products (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted first marketing approvals in 2014. As discussed in this perspective on antibodies in late-stage development, the outlook for additional approvals, potentially still in 2014 and certainly in 2015, is excellent as marketing applications for 6 antibody therapeutics (sec...

  19. Monoclonal antibodies for treating cancer

    International Nuclear Information System (INIS)

    The purpose of this study is to assess the current status of in-vivo use of monoclonal antibodies for treating cancer. Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles. More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis. The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents. As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment. 235 references

  20. Metrics for antibody therapeutics development

    OpenAIRE

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approv...

  1. Empowered Antibody Therapies - IBC conference.

    Science.gov (United States)

    Herold, Jens

    2010-10-01

    The Empowered Antibody Therapies conference, held in Burlingame, CA, USA, included topics covering new therapeutic developments in the field of multispecific antibodies. This conference report highlights selected presentations on DVD-Igs from Abbott Laboratories, ImmTACs from Immunocore, 'Dock-and-Lock' technology from Immunomedics, the bispecific BiTE antibody blinatumomab from Micromet, and Triomabs from TRION Pharma and Fresenius Biotech. PMID:20878591

  2. Rapid discovery and optimization of therapeutic antibodies against emerging infectious diseases

    OpenAIRE

    Rogers, J.; Schoepp, R J; Schröder, O; Clements, T.L.; Holland, T.F.; Li, J. Q.; Li, J.; Lewis, L.M.; Dirmeier, R.P.; Frey, G.J.; Tan, X; Wong, K.; Woodnutt, G; M. Keller; Reed, D.S.

    2008-01-01

    Using a comprehensive set of discovery and optimization tools, antibodies were produced with the ability to neutralize SARS coronavirus (SARS-CoV) infection in Vero E6 cells and in animal models. These anti-SARS antibodies were discovered using a novel DNA display method, which can identify new antibodies within days. Once neutralizing antibodies were identified, a comprehensive and effective means of converting the mouse sequences to human frameworks was accomplished using HuFR™ (human frame...

  3. Detection of Neutralising Antibody Titration in Vaccinated Owned and Stray Dogs against Rabies Virus

    OpenAIRE

    GAZİ, Aliye Ebru; AK, Seyyal

    2011-01-01

    The aim of this study was to determine the titers of neutralising antibodies against rabies virus in five hundred vaccinated owned and stray dogs within the Istanbul province. The levels of the neutralising antibody titration in the blood serum were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA) method. Sixty five (13%) of the dogs examined had adequate level (0.5 IU/ml and over) of antibody titration. Also, the effects on the formation of the neutralising antibody levels following th...

  4. Analysis of Defined Combinations of Monoclonal Antibodies in Anthrax Toxin Neutralization Assays and Their Synergistic Action

    OpenAIRE

    Ngundi, Miriam M.; Meade, Bruce D.; Little, Stephen F.; Quinn, Conrad P.; Corbett, Cindi R; Brady, Rebecca A.; Burns, Drusilla L.

    2012-01-01

    Antibodies against the protective antigen (PA) component of anthrax toxin play an important role in protection against disease caused by Bacillus anthracis. In this study, we examined defined combinations of PA-specific monoclonal antibodies for their ability to neutralize anthrax toxin in cell culture assays. We observed additive, synergistic, and antagonistic effects of the antibodies depending on the specific antibody combination examined and the specific assay used. Synergistic toxin-neut...

  5. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi;

    2014-01-01

    infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... (iii) antibody numbering and IMGT. Here, we review “antibody informatics,” which may integrate the above three fields so that bridging the gaps between industrial needs and academic solutions can be accelerated. This article is part of a Special Issue entitled: Recent advances in molecular engineering...

  6. Tumor imaging with monoclonal antibodies

    International Nuclear Information System (INIS)

    Many monoclonal antibodies directed against tumor-associated antigens have been identified, but so far none of these are tumor specific. Polyclonal and monoclonal antibodies have been used for imaging of a wide variety of tumors with success. Radiolabeling of antibody is usually done with iodine isotopes of which 123I is the best candidate for radioimmunodetection purposes. The labeling of antibodies through chelates makes it possible to use metal radioisotopes like 111In, which is the best radioisotope for imaging with monoclonal antibodies due to its favorable half-life of 2.5 days. Usually imaging cannot be performed within 24 h after injection, but clearance of antibody can be increased by using F(ab)2 of Fab. Another approach is to clear non-bound antibody by a second antibody, directed against the first. The detection limit of immunoimaging is about 2 cm, but will be improved by tomography or SPECT. There is still a high false positive and false negative rate, which makes it impossible to use radioimmunodetection as the only technique for diagnosis of tumors. In combination with other detection techniques, tumor imaging with monoclonal antibodies can improve diagnosis. 44 refs.; 3 tabs

  7. Comparative effect of Citrus sinensis and carbimazole on serum T 4 , T 3 and TSH levels

    Directory of Open Access Journals (Sweden)

    Okon Uduak Uduak

    2014-01-01

    Full Text Available Background: There are previous independent reports on the anti-thyroid property of Citrus sinensis. This isoflavones and phenolic acid-rich natural agent is widely consumed as dietary supplement, thus the need to investigate its comparative effect with a standard anti-thyroid drug on T 4 , T 3 and thyroid stimulating hormone (TSH levels. Objective: To compare the effect of Citrus sinensis and carbimazole (CARB on blood levels of thyroid hormones (T 4 and T 3 and TSH. Materials and Methods: Male wistar albino rats weighing 100-150 g were employed in this research. The rats were randomly assigned to four groups of seven rats per group. Group I served as control and were administered distilled water while groups II-IV were administered with 1500 mg/kg of Citrus sinensis (fresh orange juice; FOJ, 0.1 μg/g of levothyroxine (LVT and 0.01 mg/g of CARB, respectively, per oral once daily for 28 days. The animals were sacrificed under chloroform anaesthesia and blood sample collected by cardiac puncture and processed by standard method to obtain serum. TSH, T 4 and T 3 were assayed with the serum using ARIA II automated radioimmunoassay instrument. Results: The results showed that TSH level was significantly (P < 0.05 decreased in LVT treated group compared with the FOJ group. T 4 was significantly (P < 0.05 decreased in the FOJ and CARB groups compared with the control and LVT groups. LVT significantly increased T 4 when compared with FOJ group. T 3 was significantly (P < 0.05 decreased in the CARB group compared with the control. Conclusion: These findings suggest that FOJ alters thyroid hormones metabolism to reduce their serum levels with a compensatory elevations of TSH level in a direction similar to CARB.

  8. Antibody induction therapy for lung transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Møller, Christian H; Penninga, Ida Elisabeth Irene;

    2013-01-01

    Lung transplantation has become a valuable and well-accepted treatment option for most end-stage lung diseases. Lung transplant recipients are at risk of transplanted organ rejection, and life-long immunosuppression is necessary. Clear evidence is essential to identify an optimal, safe and effect...... effective immunosuppressive treatment strategy for lung transplant recipients. Consensus has not yet been achieved concerning use of immunosuppressive antibodies against T-cells for induction following lung transplantation....

  9. The prevalence of serum antibodies to tick-borne infections in Mbale District, Uganda: The effect of agro-ecological zone, grazing management and age of cattle

    Directory of Open Access Journals (Sweden)

    C. Rubaire-Akiiki

    2004-03-01

    Full Text Available Between August and October 2000, a cross-sectional study was conducted in smallholder dairy farms in Mbale District, Uganda to assess the prevalence of ticks and tick-borne diseases under different grazing systems and agro-ecological zones and understand the circumstances under which farmers operated. A questionnaire was administered to obtain information on dairy farm circumstances and practices. A total of 102 farms were visited and sera and ticks were collected from 478 animals. Sero-prevalence of tick-borne diseases was determined using an enzyme-linked immunoassay. Acaricides were used indiscriminately but the intensity of their use varied with the grazing system and zone. Cattle from different farms mixed for various reasons. During the dry seasons farmers have to get additional fodder from outside their farms that can result in importation of ticks. The prevalence of ticks and serum antibodies to tick-borne infections differed across the grazing systems and zones. The highest serum antibody prevalence (>60% was recorded in the lowland zone under the free range and tethering grazing systems. The lowest tick challenge and serum antibody levels (<50% were recorded in the midland and upland zones under a zero-grazing system. These findings suggest that endemic stability to East Coast Fever, babesiosis and anaplasmosis is most likely to have existed in the lowland zone, particularly, under the tethering and free-range grazing systems. Also, endemic stability for babesiosis existed in the upland zones. Endemic instability for East Coast Fever existed in the midland and upland zones. These structured observational studies are instrumental in planning of control strategies for ticks and tick borne diseases since production systems and the cattle population at high risk of the diseases in the district have been identified.

  10. The prevalence of serum antibodies to tick-borne infections in Mbale District, Uganda: the effect of agro-ecological zone, grazing management and age of cattle.

    Science.gov (United States)

    Rubaire-Akiiki, C; Okello-Onen, J; Nasinyama, G W; Vaarst, M; Kabagambe, E K; Mwayi, W; Musunga, D; Wandukwa, W

    2004-01-01

    Between August and October 2000, a cross-sectional study was conducted in smallholder dairy farms in Mbale District, Uganda to assess the prevalence of ticks and tick-borne diseases under different grazing systems and agro-ecological zones and understand the circumstances under which farmers operated. A questionnaire was administered to obtain information on dairy farm circumstances and practices. A total of 102 farms were visited and sera and ticks were collected from 478 animals. Sero-prevalence of tick-borne diseases was determined using an enzyme-linked immunoassay. Acaricides were used indiscriminately but the intensity of their use varied with the grazing system and zone. Cattle from different farms mixed for various reasons. During the dry seasons farmers have to get additional fodder from outside their farms that can result in importation of ticks. The prevalence of ticks and serum antibodies to tick-borne infections differed across the grazing systems and zones. The highest serum antibody prevalence (>60%) was recorded in the lowland zone under the free range and tethering grazing systems. The lowest tick challenge and serum antibody levels (<50%) were recorded in the midland and upland zones under a zero-grazing system. These findings suggest that endemic stability to East Coast Fever, babesiosis and anaplasmosis is most likely to have existed in the lowland zone, particularly, under the tethering and free-range grazing systems. Also, endemic stability for babesiosis existed in the upland zones. Endemic instability for East Coast Fever existed in the midland and upland zones. These structured observational studies are instrumental in planning of control strategies for ticks and tick borne diseases since production systems and the cattle population at high risk of the diseases in the district have been identified. PMID:15861224

  11. Physiopathological effects of Escherichia coli O157:H7 inoculation in weaned calves fed with colostrum containing antibodies to EspB and Intimin.

    Science.gov (United States)

    Rabinovitz, B C; Vilte, D A; Larzábal, M; Abdala, A; Galarza, R; Zotta, E; Ibarra, C; Mercado, E C; Cataldi, A

    2014-06-24

    Escherichia coli O157:H7 is responsible for severe intestinal disease and hemolytic uremic syndrome (HUS), a serious systemic complication which particularly affects children. Cattle are the primary reservoir for E. coli O157:H7 and the main source of infection for humans. In this study, we evaluated the ability of transferred maternal colostral antibodies against γ-Intimin C280 and EspB, to protect young weaned calves from E. coli O157:H7 infection. Hyperimmune colostra were obtained by immunization of pregnant cows with a mix of the mentioned antigens. All vaccinated cows mounted a significant IgG response against γ-Intimin C280, and EspB in sera and colostra. Colostrum-fed calves also exhibited high serum IgG titers against γ-Intimin C280 and EspB along with a rise in mucosal γ-Intimin C280-specific IgG antibodies at recto-anal junction and ileum. Additionally, 70 day-old calves received a challenge with E. coli O157:H7 but no reduction in total bacterial shedding or frequency of E. coli O157:H7 excretion from these calves was observed. Most tissue samples showed granulocyte focal infiltrations of the lamina propria and enterocyte erosion. In conclusion, up to the 70th day, the passively acquired γ-Intimin-C280 and EspB-IgG antibodies present in sera and recto-anal mucosa reached a titer insufficient to reduce EHEC O157 shedding and damages of experimentally inoculated young calves. PMID:24797699

  12. Autoantibodies and immunoglobulins among atomic-bomb survivors

    International Nuclear Information System (INIS)

    The purpose of this study was to determine if exposure to atomic-bomb radiation affects immune responsiveness, such as the occurrence of autoantibodies and levels of immunoglobulins. Rheumatoid factor, antinuclear antibody, antithyroglobulin antibody, anti-thyroid-microsomal antibody, and immunoglobulin levels (IgG, IgM, IgA, and IgE) were measured among 2061 Adult Health Study participants in Hiroshima and Nagasaki from December 1987 to November 1989. The prevalence and titers of rheumatoid factor increased in a statistically significant manner with increasing radiation dose. No radiation effect was found on the prevalence of antinuclear antibody, antithyroglobulin antibody, and anti-thyroid-microsomal antibody. A statistically significant relationship was also found between radiation exposure and the IgA level in females and the IgM levels in both sexes-both levels increased as radiation dose increased. However, the effects of radiation exposure were not large and accounted for less than 10% of the total variation in each measurement. Levels of IgG and IgE were not affected by radiation exposure. (author)

  13. Creating Ordered Antibody Arrays with Antibody-Polymer Conjugates

    Science.gov (United States)

    Dong, Xuehui; Obermeyer, Allie; Olsen, Bradley

    Antibodies are a category of functional proteins that play crucial roles in the immune system and have been widely applied in the area of cancer therapeutics, targeting delivery, signal detection, and sensors. Due to the extremely large size and lack of specific functional groups on the surface, it is challenging to functionalize antibodies and manipulate the ordered packing of antibodies in an array with high density and proper orientation, which is critical to achieve outstanding performance in materials. In this work, we demonstrate an efficient and facile approach for preparing antibody-polymer conjugates with two-step sequential ``click'' reaction to form antibody-polymer block copolymers. Highly ordered nanostructures are fabricated based on the principles of block copolymer self-assembly. The nanostructures are studied with both small angle X-ray scattering (SAXS) and transmission electron microscopy (TEM). Lamellae with alternating antibody domain and polymer domain are observed with an overall domain size of ~50 nm. The nanostructure not only increases the packing density and promotes proper orientation of the antibody, but also provides possible channel to facilitate substrate transportation and improves the stability of the antibody.

  14. Detection of novel diagnostic antibodies in ankylosing spondylitis: An overview.

    Science.gov (United States)

    Quaden, Dana H F; De Winter, Liesbeth M; Somers, Veerle

    2016-08-01

    Ankylosing spondylitis (AS) is a debilitating, chronic, rheumatic disease characterized by inflammation and new bone formation resulting in fusion of the spine and sacroiliac joints. Since early treatment is impeded by a delayed diagnosis, it is highly important to find new biomarkers that improve early diagnosis and may also contribute to a better assessment of disease activity, prognosis and therapy response in AS. Because of the absence of rheumatoid factor, AS was long assumed to have a seronegative character and antibodies are thus not considered a hallmark of the disease. However, emerging evidence suggests plasma cells and autoantibodies to be involved in the disease course. In this review, the role of B cells and antibodies in AS is discussed. Furthermore, an overview is provided of antibodies identified in AS up till now, and their diagnostic potential. Many of these antibody responses were based on small study populations and further validation is lacking. Moreover, most were identified by a hypothesis-driven approach and thus limited to antibodies against targets that are already known to be involved in AS pathogenesis. Hence, we propose an unbiased approach to identify novel diagnostic antibodies. The already successfully applied techniques cDNA phage display and serological antigen selection will be used to identify antibodies against both known and new antigen targets in AS plasma. These newly identified antibodies will enhance early diagnosis of AS and provide more insight into the underlying disease pathology, resulting in a more effective treatment strategy and eventually an improved disease outcome. PMID:27288842

  15. Effects of clonal variation on growth, metabolism, and productivity in response to trophic factor stimulation: a study of Chinese hamster ovary cells producing a recombinant monoclonal antibody

    OpenAIRE

    Dahodwala, Hussain; Nowey, Mark; Mitina, Tatyana; Sharfstein, Susan T.

    2011-01-01

    The growth, metabolism, and productivity of five Chinese hamster ovary (CHO) clones were explored in response to stimulation with insulin (5 mg/L) and LONG®R3IGF-I (20 μg/L or 100 μg/L). All five clones were derived from the same parental CHO cell line (DG44) and produced the same recombinant monoclonal antibody, with varying specific productivities. There was no uniform response among the clones to stimulation with the different trophic factors. One of the high productivity clones (clone D) ...

  16. Imaging cancer using PET - the effect of the bifunctional chelator on the biodistribution of a {sup 64}Cu-labeled antibody

    Energy Technology Data Exchange (ETDEWEB)

    Dearling, Jason L.J., E-mail: jason.dearling@childrens.harvard.ed [Division of Nuclear Medicine and Department of Radiology, Children' s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Voss, Stephan D. [Division of Nuclear Medicine and Department of Radiology, Children' s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Dunning, Patricia; Snay, Erin [Division of Nuclear Medicine and Department of Radiology, Children' s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115 (United States); Fahey, Frederic [Division of Nuclear Medicine and Department of Radiology, Children' s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States); Smith, Suzanne V. [Australian National Science and Technology Organisation (ANSTO), New Illawarra Road, PMB1, Menai, New South Wales 2234 (Australia); Huston, James S. [EMD Serono Research Center, 45A Middlesex Turnpike, Billerica, MA 01821-3936 (United States); Boston Biomedical Research Institute, Watertown, MA 02472-2899 (United States); Meares, Claude F. [Department of Chemistry, University of California, One Shields Avenue, Davis, CA 95616-5295 (United States); Treves, S. Ted; Packard, Alan B. [Division of Nuclear Medicine and Department of Radiology, Children' s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115 (United States); Harvard Medical School, Boston, MA 02115 (United States)

    2011-01-15

    Introduction: Use of copper radioisotopes in antibody radiolabeling is challenged by reported loss of the radionuclide from the bifunctional chelator used to label the protein. The objective of this study was to investigate the relationship between the thermodynamic stability of the {sup 64}Cu-complexes of five commonly used bifunctional chelators (BFCs) and the biodistribution of an antibody labeled with {sup 64}Cu using these chelators in tumor-bearing mice. Methods: The chelators [S-2-(aminobenzyl)1,4,7-triazacyclononane-1,4,7-triacetic acid (p-NH{sub 2}-Bn-NOTA): 6-[p-(bromoacetamido)benzyl]-1, 4, 8, 11-tetraazacyclotetradecane-N, N', N'', N'''-tetraacetic acid (BAT-6): S-2-(4-aminobenzyl)-1,4,7,10-tetraazacyclododocane tetraacetic acid (p-NH{sub 2}-Bn-DOTA): 1,4,7,10-tetraazacyclododocane-N, N', N', N''-tetraacetic acid (DOTA): and 1-N-(4-aminobenzyl)-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1, 8-diamine (SarAr)] were conjugated to the anti-GD2 antibody ch14.18, and the modified antibody was labeled with {sup 64}Cu and injected into mice bearing subcutaneous human melanoma tumors (M21) (n = 3-5 for each study). Biodistribution data were obtained from positron emission tomography images acquired at 1, 24 and 48 hours post-injection, and at 48 hours post-injection a full ex vivo biodistribution study was carried out. Results: The biodistribution, including tumor targeting, was similar for all the radioimmunoconjugates. At 48 h post-injection, the only statistically significant differences in radionuclide uptake (p < 0.05) were between blood, liver, spleen and kidney. For example, liver uptake of [{sup 64}Cu]ch14.18-p-NH{sub 2}-Bn-NOTA was 4.74 {+-} 0.77 per cent of the injected dose per gram of tissue (%ID/g), and for [{sup 64}Cu]ch14.18-SarAr was 8.06 {+-} 0.77 %ID/g. Differences in tumor targeting correlated with variations in tumor size rather than which BFC was used. Conclusions: The results of this

  17. Most Anti-BrdU Antibodies React with 2′-Deoxy-5-Ethynyluridine — The Method for the Effective Suppression of This Cross-Reactivity

    Czech Academy of Sciences Publication Activity Database

    Liboska, Radek; Ligasová, Anna; Strunin, Dmytro; Rosenberg, Ivan; Koberna, Karel

    2012-01-01

    Roč. 7, č. 12 (2012), e51679/1-e51679/10. E-ISSN 1932-6203 R&D Projects: GA AV ČR KAN200520801; GA ČR GBP302/12/G157 Grant ostatní: GA ČR(CZ) GA204/09/0973 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514; CEZ:AV0Z50040702 Keywords : 2´-deoxy-5-ethynyluridine * 5-bromo-2´-deoxyuridine * DNA replication * anti-BrdU antibodies * immunocytochemistry Subject RIV: CC - Organic Chemistry Impact factor: 3.730, year: 2012

  18. Measles vaccination in the presence or absence of maternal measles antibody

    DEFF Research Database (Denmark)

    Aaby, Peter; Martins, Cesário L; Garly, May-Lill;

    2014-01-01

    BACKGROUND: Measles vaccine (MV) has a greater effect on child survival when administered in early infancy, when maternal antibody may still be present. METHODS: To test whether MV has a greater effect on overall survival if given in the presence of maternal measles antibody, we reanalyzed data...... measles antibody and 14.5 per 1000 person-years without measles antibody (MRR, 0.29; 95% CI, .09-.91). Possible confounding factors did not explain the difference. In a combined analysis, children who had measles antibody detected when they received their first dose of MV at 4-6 months of age had lower...

  19. 输血患者1337例行意外抗体筛检临床研究%Research on the Effect of 1337 Patients with Transfusion Undergoing Unexpected Antibody Screening

    Institute of Scientific and Technical Information of China (English)

    鲁石; 罗薛莲

    2015-01-01

    positive detection rate of patients with pregnancy history was lower than that of patients without pregnancy history (0.06% vs 2.66%, P<0.05),and the positive detection rate of once transfusion was 0.14%,and of two and three times of transfusion was 1.86% and 2.60% respectively,and the positive detection rate of patients with once transfu-sion was lower than that of patients with two and three times of transfusions , and the transfusion reaction occurrence rate of the observation was significantly lower than that of the control group (0.07% vs 2.02%,P<0.05 ) .Conclusion Multiple transfusions and pregnancy may produce unexpected antibody in transfu-sion,and patients undergoing unexpected antibody screening prior to the transfusion can effectively improve the safety of transfusion.

  20. The antiphospholipid antibody syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Luma HN

    2012-10-01

    Full Text Available Henry Namme Luma,1,2 Marie-Solange Doualla,1,2 Elvis Temfack,1 Servais Albert Fiacre Eloumou Bagnaka,1 Emmanuella Wankie Mankaa,3 Dobgima Fofung41Department of Internal Medicine, Douala General Hospital, Douala, Cameroon; 2Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon; 3Department of Radiology, Douala General Hospital Douala, Cameroon; 4Department of Abdominal Surgery, Daniel Muna Memorial Clinic, Douala, CameroonAbstract: Antiphospholipid antibody syndrome is defined by the presence of thromboembolic complications and/or pregnancy morbidity in the presence of persistently increased titers of antiphospholipid antibodies. Its clinical presentation can be diverse and any organ can be involved, with a current impact in most surgical and medical specialties. The authors present the case of a 43-year-old man who, over a 13-year period of follow-up, presented with thrombosis of the mesenteric vein, inferior vena cava, and axillary and subclavian veins in a setting where diagnostic and therapeutic options are limited and costly. Through this case report, the authors aim to describe the evolution of this complex pathology, which to date has not been described in the authors' milieu – probably because of its challenging diagnosis and the limited treatment options available. The authors conclude that clinicians need to have a high index of suspicion of APS in patients who present with a thrombotic episode – clinicians should investigate for the presence of antiphospholipid antibodies, as early diagnosis may influence the course of the disease. Furthermore, resources for the detection of antiphospholipid antibodies should be made readily available in resource-limited settings. Finally, patient education on the importance of drug compliance, periodic monitoring, and prevention of thrombosis is indispensable, especially as mortality could be associated with the effects of vascular thrombosis and/or the effects

  1. Conformational Isomerism Can Limit Antibody Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Debler, E.W.; Muller, R.; Hilvert, D.; Wilson, I.A.

    2009-05-14

    Ligand binding to enzymes and antibodies is often accompanied by protein conformational changes. Although such structural adjustments may be conducive to enzyme catalysis, much less is known about their effect on reactions promoted by engineered catalytic antibodies. Crystallographic and pre-steady state kinetic analyses of antibody 34E4, which efficiently promotes the conversion of benzisoxazoles to salicylonitriles, show that the resting catalyst adopts two interconverting active-site conformations, only one of which is competent to bind substrate. In the predominant isomer, the indole side chain of Trp{sup L91} occupies the binding site and blocks ligand access. Slow conformational isomerization of this residue, on the same time scale as catalytic turnover, creates a deep and narrow binding site that can accommodate substrate and promote proton transfer using Glu{sup H50} as a carboxylate base. Although 34E4 is among the best catalysts for the deprotonation of benzisoxazoles, its efficiency appears to be significantly limited by this conformational plasticity of its active site. Future efforts to improve this antibody might profitably focus on stabilizing the active conformation of the catalyst. Analogous strategies may also be relevant to other engineered proteins that are limited by an unfavorable conformational pre-equilibrium.

  2. Nano antibody therapy for cancer

    International Nuclear Information System (INIS)

    Nanomedicine, an offshoot of nanotechnology, refers to highly specific medical intervention at the molecular scale for curing disease or repairing damaged tissues, such as bone, muscle, or nerve. Nanotechnology can have an early, paradigm-changing impact on how clinicians will detect cancer in its earliest stages. Exquisitely sensitive devices constructed of nanoscale components-such as nanocantilevers, nanowires and nanochannels-offer the potential for detecting even the rarest molecular signals associated with malignancy. One of the most pressing needs in clinical oncology is for imaging agents that can identify tumors that are far smaller than is possible with today's technology, at a scale of 100,000 cells rather than 1,000,000,000 cells. A new approach in nanotechnology for treating cancer incorporates nano iron particles and attaches them to an antibody that has targets only cancer cells and not healthy cells. The treatment works in two steps. This treatment is an ingenious way to make localized tumor ablation a systemic treatment. The advantages are incredible. There are absolutely no side effects from this treatment. It is not painful or even uncomfortable. The iron particles get flushed harmlessly from the body. It is not a drug and so the cancer cannot build up a resistance to the treatment. It is a systematic treatment; even cancer cells and tumors that are not known about get heated up and ablated. This treatment can even be used to enhance imaging of the cancer because once the cancer cells are coated with the iron particles, they are easy to identify. Everything depends on how reliably the antibodies target cancer cells and not healthy cells. When used in conjunction with other systemic treatments, such as vaccine treatments, we could be looking at a time when even advanced cancers can be brought under control. (author)

  3. Cell attachment to frozen sections of injured adult mouse brain: effects of tenascin antibody and lectin perturbation of wound-related extracellular matrix molecules.

    Science.gov (United States)

    Laywell, E D; Friedman, P; Harrington, K; Robertson, J T; Steindler, D A

    1996-06-01

    Previous studies describing the use of cryoculture methods have focused on the efficacy of the method for studying neuron attachment and neurite outgrowth on intact sections of nerve, and rodent and even human brain. The cryoculture method has shown promise for determining the presence of cell attachment- and neurite-growth-inhibiting molecules in such specimens, and some studies have also attempted to neutralize such molecules with antibodies to myelin inhibitory proteins, nerve growth factor, or factors present in conditioned media that may counteract the repulsiveness of some of these molecules preserved in sections of, for example, myelinated nerves or adult brain white matter. The present study describes the novel use of lesioned central nervous system cryocultures as substrates for investigating the attachment of embryonic neurons and PC12 cells. In addition to demonstrating the use of this novel scar substrate to extend previous 'scar-in-a-dish' models (David et al. (1990) Neuron, 5:463-469; Rudge and Silver (1990) J. Neurosci., 10: 3594-3603; Rudge et al. (1989) Exp. Neurol., 103: 1-16), the present study also describes antibody and lectin perturbations of putative inhibitory molecules that result in an enhanced attachment of cells to cryosection cultures of brain and spinal cord wounds. PMID:8835793

  4. Itolizumab – a humanized anti-CD6 monoclonal antibody with better side effects profile for the treatment of psoriasis [Corrigendum

    Directory of Open Access Journals (Sweden)

    Menon R

    2015-06-01

    Full Text Available Menon R, David BG. Clinical, Cosmetic and Investigational Dermatology. 2015;8:215–22.On page 215, please note correspondence should have been listed as:   Roshni Menon, D II/17,JIPMER Campus, Dhanvanthri Nagar,Pondicherry, India 605006Tel +91 944 320 8140Email roshnijagdish@gmail.com.On page 215, the first sentence of the Introduction was “Psoriasis is a chronic inflammatory disease of the skin characterized by exacerbations and remissions affecting 1%–3% of the world’s population, and approximately 20% of patients have moderate to severe disease.1,2” however should have been “Psoriasis is a chronic inflammatory disease of the skin characterized by exacerbations and remissions affecting 1%–3% of the world’s population. Approximately 20% of patients have moderate to severe disease.1,2”On page 217, 219, and 221 the running header was “Itolizumab – aCD6 monoclonal antibody for the treatment of psoriasis” however should have been “Itolizumab – a humanized anti CD6 monoclonal antibody for the treatment of psoriasis”.On page 218, Table 1, the second column heading was listed as “Anand et al25 n=40 (moderate–severe psoriasis” however should have been “Anand et al25 n=40/32 weeks (moderate–severe psoriasis”.Read the original article 

  5. Treatment of leukemia with radiolabeled monoclonal antibodies.

    Science.gov (United States)

    Sgouros, G; Scheinberg, D A

    1993-01-01

    In contrast to radioimmunotherapy of solid disease, wherein the primary obstacle to success is access of radiolabeled antibody to antigen-positive cells, in the treatment of leukemia delivering a lethal absorbed dose to the isolated cell appears to be the primary obstacle. The isolated cell is defined as one that is exposed only to self-irradiation (from internalized or surface-bound radiolabeled antibody) and to irradiation from free antibody in the blood. It is isolated in the sense that the particulate (beta, electron, alpha) emissions from its nearest neighboring antigen-positive cell do not contribute to its absorbed dose. Disease in the bone marrow and other tissues, since it is confined to a smaller volume, is more easily eradicated because the absorbed dose to a given cell nucleus is enhanced by emissions from adjacent cells (a smaller fraction of the emission energy is 'wasted'). The optimization simulations presented above for the M195 antibody suggest that the optimum dose of antibody that should be administered is that required to yield a concentration within the distribution volume of the antibody that is approximately equal to the concentration of antigen sites as determined by the tumor burden. Although not specifically considered in the modeling example presented above, antibody internalization and catabolism may be expected to play an important role in radioimmunotherapy treatment planning of leukemia. Depending upon the kinetics of internalization and catabolism, the absorbed dose to the red marrow and to antigen-positive cells may be reduced considerably, since catabolism, assuming that it is followed by rapid extrusion of the radioactive label, would decrease the cells' exposure time considerably. The recently demonstrated effectiveness of radioimmunotherapy in certain cases of B-cell lymphoma and in reducing tumor burden in acute myelogenous leukemia suggests that radioimmunotherapy is beginning to fulfill the promise held when it was initially

  6. Targeting of Antibodies using Aptamers

    OpenAIRE

    Missailidis, Sotiris

    2003-01-01

    The chapter presents a methodology for the rapid selection of aptamers against antibody targets. It is a detailed account of the various methodological steps that describe the selection of aptamers, including PCR steps, buffers to be used, target immobilisation, partitioning and amplification of aptamers, clonning and sequencing, to results in high affinity and specificity ligands for the chosen target antibody.

  7. Refolding Technologies for Antibody Fragments

    OpenAIRE

    Tsutomu Arakawa; Daisuke Ejima

    2014-01-01

    Refolding is one of the production technologies for pharmaceutical grade antibody fragments. Detergents and denaturants are primarily used to solubilize the insoluble proteins. The solubilized and denatured proteins are refolded by reducing the concentration of the denaturants or detergents. Several refolding technologies have been used for antibody fragments, comprising dilution, dialysis, solid phase solvent exchange and size exclusion chromatography, as reviewed here. Aggregation suppresso...

  8. ANTISPERM ANTIBODIES IN VASOVASOSTOMY

    Directory of Open Access Journals (Sweden)

    Gholamreza Pourmand

    1993-06-01

    Full Text Available Two hundred and forty patients, who had undergone vasectomy from 1977 to 1985 and subsequent vasovasostomy ,were studied for the presence of sperm-specific antibodies by using the Kibrick's gelatin agglutination test. The number of successful pregnancies and the presence of agglutination were also considered in this survey. Sixty-nine pregnancies occurred in total and agglutination was present in 49% out of 51% positive specimens by the Kibrick Test."nThe average sperm motility was slightly higher in the negative Kibrick group than in the positive Kibrick group. The obtained data indicated that there seems to be a relationship between the increased titers and percentage of agglutination in semen samples.

  9. Conjugation of R-Phycoerythrin to a Polyclonal Antibody and F (ab')2 Fragment of a Polyclonal Antibody by Two Different Methods.

    Science.gov (United States)

    Mahmoudian, Jafar; Jeddi-Tehrani, Mahmood; Rabbani, Hodjattallah; Mahmoudi, Ahmad Reza; Akhondi, Mohammad Mehdi; Zarnani, Amir Hassan; Goli, Leila Balaei; Babaei, Mahdokht; Ghods, Roya

    2010-04-01

    R-Phycoerythrin (R-PE), a fluorescent protein from phycobiliprotein family, is isolated from red algae. Conjugation of antibodies to R-PE facilitates multiple fluorescent staining methods. In the present study polyclonal antibodies and polyclonal F(ab')2 fragment antibodies were conjugated to R-PE by two different methods. The efficiency of the methods was evaluated using Immunocytochemistry (ICC) and Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE). In the first conjugation method, PE was attached to SMCC linker followed by conjugation of antibody to PE-SMCC. In the second method, SH groups were added onto R-PE molecule, while the antibody was attached to SPDP linker. Then, the antibody-SPDP molecule was conjugated to R-PE. Our results showed that the two conjugation methods did not have any abrogative effects on the antibody binding activity. PMID:23407609

  10. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed. PMID:20930555

  11. Quantitative assessment of antibody internalization with novel monoclonal antibodies against Alexa fluorophores.

    Science.gov (United States)

    Liao-Chan, Sindy; Daine-Matsuoka, Barbara; Heald, Nathan; Wong, Tiffany; Lin, Tracey; Cai, Allen G; Lai, Michelle; D'Alessio, Joseph A; Theunissen, Jan-Willem

    2015-01-01

    Antibodies against cell surface antigens may be internalized through their specific interactions with these proteins and in some cases may induce or perturb antigen internalization. The anti-cancer efficacy of antibody-drug conjugates is thought to rely on their uptake by cancer cells expressing the surface antigen. Numerous techniques, including microscopy and flow cytometry, have been used to identify antibodies with desired cellular uptake rates. To enable quantitative measurements of internalization of labeled antibodies, an assay based on internalized and quenched fluorescence was developed. For this approach, we generated novel anti-Alexa Fluor monoclonal antibodies (mAbs) that effectively and specifically quench cell surface-bound Alexa Fluor 488 or Alexa Fluor 594 fluorescence. Utilizing Alexa Fluor-labeled mAbs against the EphA2 receptor tyrosine kinase, we showed that the anti-Alexa Fluor reagents could be used to monitor internalization quantitatively over time. The anti-Alexa Fluor mAbs were also validated in a proof of concept dual-label internalization assay with simultaneous exposure of cells to two different mAbs. Importantly, the unique anti-Alexa Fluor mAbs described here may also enable other single- and dual-label experiments, including label detection and signal enhancement in macromolecules, trafficking of proteins and microorganisms, and cell migration and morphology. PMID:25894652

  12. Quantitative assessment of antibody internalization with novel monoclonal antibodies against Alexa fluorophores.

    Directory of Open Access Journals (Sweden)

    Sindy Liao-Chan

    Full Text Available Antibodies against cell surface antigens may be internalized through their specific interactions with these proteins and in some cases may induce or perturb antigen internalization. The anti-cancer efficacy of antibody-drug conjugates is thought to rely on their uptake by cancer cells expressing the surface antigen. Numerous techniques, including microscopy and flow cytometry, have been used to identify antibodies with desired cellular uptake rates. To enable quantitative measurements of internalization of labeled antibodies, an assay based on internalized and quenched fluorescence was developed. For this approach, we generated novel anti-Alexa Fluor monoclonal antibodies (mAbs that effectively and specifically quench cell surface-bound Alexa Fluor 488 or Alexa Fluor 594 fluorescence. Utilizing Alexa Fluor-labeled mAbs against the EphA2 receptor tyrosine kinase, we showed that the anti-Alexa Fluor reagents could be used to monitor internalization quantitatively over time. The anti-Alexa Fluor mAbs were also validated in a proof of concept dual-label internalization assay with simultaneous exposure of cells to two different mAbs. Importantly, the unique anti-Alexa Fluor mAbs described here may also enable other single- and dual-label experiments, including label detection and signal enhancement in macromolecules, trafficking of proteins and microorganisms, and cell migration and morphology.

  13. Incidence of radiation-induced Graves' disease in patients treated with radioiodine for thyroid autonomy before and after introduction of a high-sensitivity TSH receptor antibody assay

    Energy Technology Data Exchange (ETDEWEB)

    Dunkelmann, Simone; Wolf, Ricarda; Koch, Annedore; Kittner, Christian; Groth, Peter; Schuemichen, Carl [University of Rostock, Clinic of Nuclear Medicine, Rostock (Germany)

    2004-10-01

    Autoimmune hyperthyroidism may occur several months after radioiodine therapy (RIT) for functional thyroid autonomy. Exacerbation of pre-existing subclinical Graves' disease (GD) has been held responsible for this phenomenon. Determination of TSH receptor antibody using solubilised porcine epithelial cell membranes is insensitive and may have failed to diagnose GD in these patients before RIT. Following the introduction of a more sensitive assay, using the human TSH receptor as an antigen, it has been expected that the incidence of radiation-induced GD after RIT for functional thyroid autonomy will be reduced. In a first group of 1,428 patients treated between November 1993 and March 1997 (group I) we used the porcine TRAb assay to exclude GD, while in a second group comprising 1,408 patients treated between January 2000 and December 2001 (group II), GD was excluded using the human TRAb assay. A matched control group of 231 patients was derived from group II. In group I a total of 15 (1.05%) patients developed obvious or suspected radiation-induced GD, while in group II 17 (1.2%) did so; the interval until development of GD was 8.4 and 8.8 months, respectively, after RIT. Serum anti-thyroid peroxidase levels before RIT were elevated in 36.4% of group I patients and 47.1% of group II patients, but in only 5.6% of the control group. Other non-specific signs of mild immunopathy of the thyroid were seen retrospectively in 73.3%, 64.7% and 16.0% of the patients in these three groups, respectively. In conclusion, the introduction of a high-sensitivity TRAb assay did not reduce the incidence of autoimmune hyperthyroidism occurring late after RIT for functional thyroid autonomy, but mild immunopathy of the thyroid is seen more frequently in these patients and seems to be a predisposing factor in the development of radiation-induced GD. (orig.)

  14. Epstein-Barr virus antibody test

    Science.gov (United States)

    EBV antibody test; EBV serology ... a lab, where a lab specialist looks for antibodies to the Epstein-Barr virus. In the first stages of an illness, little antibody may be detected. For this reason, the test ...

  15. Measurement of antibodies to tubulin by radioimmunoassay

    International Nuclear Information System (INIS)

    A solid-phase double antibody radioimmunoassay capable of measuring antibody to tubulin, the principal component of microtubules, is described. This assay is simple, combining sensitivity with specificity and also allowing determination of antibody subclasses. (Auth.)

  16. Antibodies - Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    NCI announces the release of monoclonal antipeptide antibodies from rabbit for distribution on the antibody portal. There are 60 recently added monoclonal antibodies, with 56 generated from mouse and 4 generated from rabbit.

  17. Treating multiple sclerosis with monoclonal antibodies: a 2013 update.

    Science.gov (United States)

    Deiß, Annika; Brecht, Isabel; Haarmann, Axel; Buttmann, Mathias

    2013-03-01

    The third part of this in-depth review series on the treatment of multiple sclerosis (MS) with monoclonal antibodies covers the years 2010-2012. The natalizumab section gives a progressive multifocal leukoencephalopathy update, focusing on clinically relevant aspects. Furthermore, it outlines problems around natalizumab cessation and current evidence on therapeutic strategies thereafter. Finally, it reviews evidence on Janus-faced modes of natalizumab action besides anti-inflammatory effects, including proinflammatory effects. The section on alemtuzumab critically analyzes recent Phase III results and discusses which patients might be best suited for alemtuzumab treatment, and reviews the long-term immunological impact of this anti-CD52 antibody. The daclizumab section critically summarizes results from the Phase IIb SELECT/SELECTION trial and introduces the Phase III program. The section on anti-CD20 antibodies reviews Phase II results on ocrelizumab and ofatumumab, and discusses current perspectives of these antibodies for MS therapy. Promising recent Phase II results on the anti-IL-17A antibody secukinumab (AIN457) are outlined and a short update on tabalumab (LY2127399) is given. Other highlighted antibodies currently being tested in MS patients include GNbAC1, BIIB033, MOR103 and MEDI-551. Finally, the authors give an update on the role monoclonal antibodies could play in the therapeutic armamentarium for MS in the medium term. PMID:23448220

  18. Egg yolk IgY: protection against rotavirus induced diarrhea and modulatory effect on the systemic and mucosal antibody responses in newborn calves.

    Science.gov (United States)

    Vega, C; Bok, M; Chacana, P; Saif, L; Fernandez, F; Parreño, V

    2011-08-15

    Bovine rotavirus (BRV) is an important cause of diarrhea in newborn calves. Local passive immunity is the most efficient protective strategy to control the disease. IgY technology (the use of chicken egg yolk immunoglobulins) is an economic and practical alternative to prevent BRV diarrhea in dairy calves. The aim of this study was to evaluate the protection and immunomodulation induced by the oral administration of egg yolk enriched in BRV specific IgY to experimentally BRV infected calves. All calves in groups Gp 1, 2 and 3 received control colostrum (CC; BRV virus neutralization Ab titer - VN=65,536; ELISA BRV IgG(1)=16,384) prior to gut closure. After gut closure, calves received milk supplemented with 6% BRV-immune egg yolk [(Gp 1) VN=2048; ELISA IgY Ab titer=4096] or non-immune control egg yolk [(Gp 2) VNcolostrum deprived calves (CD) fed antibody (Ab) free milk served as controls (Gp 3 and 4, respectively). Calves were inoculated with 10(5.85)focus forming units (FFU) of virulent BRV IND at 2 days of age. Control calves (Gp 3 and 4) and calves fed control IgY (Gp 2) were infected and developed severe diarrhea. Around 80% calves in Gp 1 (IgY 4096) were infected, but they showed 80% (4/5) protection against BRV diarrhea. Bovine RV-specific IgY Ab were detected in the feces of calves in Gp 1, indicating that avian antibodies (Abs) remained intact after passage through the gastrointestinal tract. At post infection day 21, the duodenum was the major site of BRV specific antibody secreting cells (ASC) in all experimental groups. Mucosal ASC responses of all isotypes were significantly higher in the IgY treated groups, independently of the specificity of the treatment, indicating that egg yolk components modulated the immune response against BRV infection at the mucosal level. These results indicate that supplementing newborn calves' diets for the first 14 days of life with egg yolk enriched in BRV-specific IgY represents a promising strategy to prevent BRV

  19. Characterization of a Novel Monoclonal Antibody to Human Stem Cell Factor and its Determination Effect on Ex Vivo Stem Cell Expansion

    Institute of Scientific and Technical Information of China (English)

    Jie Fan; Ding Xinxin; Jiang Yongping

    2013-01-01

    Background:Hematopoietic stem cell (HSC) transplantation can be used to treat blood and immune system disorders. Fresh umbilical cord blood (UCB), a major source of HSC for potential clinical applications, contains a limited number of HSCs. Stem cell factor (SCF) activates HSC self-renewal and is being used to stimulate ex vivo expansion of HSCs for treating various hematologic diseases in clinic. Yet, the mechanism by which SCF stimulates and supports HSCs expansion remains poorly understood. Thus, the purpose of the study is to obtain novel monoclonal antibodies for structural and functional SCF characterizations, as well as for the optimization of HSCs ex vivo expansion. Methods:Recombinant human stem cell factor (rhSCF) was used for producing monoclonal antibody (mAb). High-titer mAb speciifc to rhSCF was selected by following immunochemical screening to various mAb cell lines. HSCs with CD34+ epitope were isolated from UCB using affinity chromatography. SCF activity was tested in an ex vivo HSC expansion assay, with use of flow cytometry for detection of CD34+ cell and total mononuclear cells. Part of rhSCF that contained the antibody-binding site was identified via immunoblot analysis of rhSCF tryptic peptides, rhSCF-speciifc mAb, and subsequent NH2-terminal amino acid sequence analysis of the detected peptides. Results: The mAb cell line 23C8 with a high titer was found to be speciifc for rhSCF. In ex vivo cord blood expansion assays, the ability of rhSCF to stimulate the expansion of CD34+ cells was significantly inhibited by 23C8 in a dose-dependet fashion(?). Through peptide mapping, the binding site of 23C8 on rhSCF was mapped to the ifrst 104 amino acids.. Conclusion: The mAb cell line 23C8 produces speciifc and inhibitory anti-rhSCF mAb. The mAb appears to bind directly to a part of rhSCF that is critical for biological activity. This functionally active site of rhSCF is located in the ifrst 104 amino acids from the NH2-terminus. The novel anti

  20. Human recombinant TSH preceding a therapeutic dose of radioiodine for multinodular goiters has no significant effect in the surge of TSH-receptor and TPO antibodies.

    Science.gov (United States)

    Rubio, Ileana G S; Perone, Bruno H; Silva, Marcia N C; Knobel, Meyer; Medeiros-Neto, Geraldo

    2005-02-01

    Radioiodine (RAI) treatment has increasingly been used mostly in elderly patients with multinodular goiter (MNG) as an alternative for surgery. Recombinant human thyrotropin (rhTSH) has been demonstrated to increase the uptake of RAI and also to promote a more even distribution of radionuclide among the various nodules. We have compared the surge of autoantibodies to thyroid peroxidase (anti-TPO) and to the TSH receptor (TRAb) in two groups of patients with MNG. Group RAI (n = 15) received only RAI, and Group RAI+rhTSH (n = 15) received RAI 24 h after 0.45 mg of rhTSH intramuscularly. At baseline, all 30 patients had negative anti-TPO antibodies. After RAI, 16 patients (eight in each group) exhibited a positive anti-TPO test (range, 70-2359 U/mL). In the rhTSH-treated group, anti-TPO values were significantly higher (as compared to basal levels; p test at baseline (67.5% inhibition of the TSH binding). After RAI, positive TRAb values were present in 21/30 patients. After 6 months of RAI treatment, there was a significant increase of the TRAb values in Group RAI+rhTSH patients. After 12 months, only four patients had positive TRAb (Group RAI: three patients; Group RAI+rhTSH: one patient). Two patients, one of each group, had an elevation of free T4 levels and suppressed serum TSH values, indicating hyperthyroidism (Graves' disease). Bioassay of TSH receptor (TSHR) indicated absence of a significant elevation of cAMP in the medium before and after RAI treatment in all patients. Moreover, predominantly blocking TSHR autoantibodies were detected in six of the 30 patients (three of each group). Sera from these patients were able to reduce the TSH-stimulated cAMP generation by CHO cells. We conclude that the autoantibodies to the TSHR and to TPO may occur after RAI treatment of patients, either with or without previous stimulation by rhTSH. The antibodies to the TSH comprised a combination of agonist (stimulating) and antagonist (blocking) antibodies, which in most

  1. Immunity to rhabdoviruses in rainbow trout: the antibody response

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lapatra, S.E.

    1999-01-01

    occasional detrimental effect on rainbow trout farming. Research efforts have been focused on understanding the mechanisms involved in protective immunity. Several specific and nonspecific cellular and humoral parameters are believed to be involved, but only the antibody response has been characterised in......, have demonstrated that rainbow trout can produce specific and highly functional antibodies that are able to neutralise virus pathogenicity in vitro as well as in vivo. The apparently more restricted antibody response to IHNV and VHSV antigens in fish compared to mammals could possibly be explained by...

  2. Heterohybridoma for the production of non murine monoclonal antibodies

    Directory of Open Access Journals (Sweden)

    Kh.Victoria Chanu and M. Ayub Ali

    Full Text Available Hybridoma technology described by kohler and Milstein produce only mouse immunoglobulins. Such immunoglobulins have limited use due to its negative side effects such as the recipient’s immune response. The production of a non murine monoclonal antibody to combat the problems of murine monoclonal antibody is again difficult due to the lack of a suitable myeloma cell line. Heterohybridoma formed by the fusion of lymphocyte of one species with the myeloma cell of a different species is the solution, which can be used for the production of non murine monoclonal antibodies. [Veterinary World 2010; 3(8.000: 390-392

  3. Effect of yeast-derived products and distillers dried grains with solubles (DDGS) on antibody-mediated immune response and gene expression of pattern recognition receptors and cytokines in broiler chickens immunized with T-cell dependent antigens.

    Science.gov (United States)

    Alizadeh, M; Rodriguez-Lecompte, J C; Echeverry, H; Crow, G H; Slominski, B A

    2016-04-01

    This study evaluated the effect of yeast-derived products on innate and antibody mediated immune response in broiler chickens following immunization with sheep red blood cells (SRBC) and bovine serum albumin (BSA). One-day-old male broiler chickens (Ross-308) were randomly assigned to 6 dietary treatments of 9 replicate cages of 5 birds each per treatment. Dietary treatments consisted of a Control diet without antibiotic, and diets containing 11 mg/kg of virginiamycin, 0.25% of yeast cell wall (YCW), 0.2% of a commercial product Maxi-Gen Plus containing processed yeast and nucleotides, 0.05% of nucleotides, or a diet containing 10% of DDGS. On days 21 and 28 post-hatching, 5 birds per treatment were immunized intramuscularly with both SRBC and BSA. One week after each immunization, blood samples were collected. Serum samples were analyzed by hemagglutination test for antibody response to SRBC, and by ELISA for serum IgM and IgG response to BSA. On d 35, 5 birds per treatment were euthanized and the tissue samples from the cecal tonsils were collected to assess the gene expression of toll-like receptors TLR2b, TLR4, and TLR21, monocyte mannose receptor (MMR), and cytokines IL-10, IL-13, IL-4, IL-12p35, and IFN-γ. The results for gene expression analysis demonstrated that the diet supplemented with YCW increased the expression of TLR2b and T-helper type 2 cytokines IL-10, IL-4, and IL-13 relative to the Control; and the expression of TLR4 and IL-13 was upregulated in the nucleotide-containing diet. However, the diets containing antibiotics or Maxi-Gen Plus downregulated the expression of IFN-γ compared to the control. The primary antibody response to SRBC was not affected by diets. However, the diet containing YCW increased the secondary antibody response to SRBC compared to the antibiotic treatment. Neither primary nor secondary IgG and IgM response against BSA were affected by diets. In conclusion, supplementation of the diet with YCW stimulated Th2 cell

  4. Targeting FcRn for the modulation of antibody dynamics.

    Science.gov (United States)

    Ward, E Sally; Devanaboyina, Siva Charan; Ober, Raimund J

    2015-10-01

    The MHC class I-related receptor, FcRn, is a multitasking protein that transports its IgG ligand within and across cells of diverse origins. The role of this receptor as a global regulator of IgG homeostasis and transport, combined with knowledge of the molecular details of FcRn-IgG interactions, has led to opportunities to modulate the in vivo dynamics of antibodies and their antigens through protein engineering. Consequently, the generation of half-life extended antibodies has shown a rapid expansion over the past decade. Further, FcRn itself can be targeted by inhibitors to induce decreased levels of circulating IgGs, which could have applications in multiple clinical settings. The engineering of antibody-antigen interactions to reduce antibody-mediated buffering of soluble ligand has also developed into an active area of investigation, leading to novel antibody platforms designed to result in more effective antigen clearance. Similarly, the target-mediated elimination of antibodies by internalizing, membrane bound antigens (receptors) can be decreased using novel engineering approaches. These strategies, combined with subcellular trafficking analyses of antibody/antigen/FcRn behavior in cells to predict in vivo behavior, have considerable promise for the production of next generation therapeutics and diagnostics. PMID:25766596

  5. Mechanisms of Mitochondrial Damage in Keratinocytes by Pemphigus Vulgaris Antibodies*

    OpenAIRE

    Kalantari-Dehaghi, Mina; Chen, Yumay; Deng, Wu; Chernyavsky, Alex; Marchenko, Steve; Wang, Ping H.; Grando, Sergei A.

    2013-01-01

    Background: Previous studies suggested that mitochondrial antibodies contribute to pemphigus vulgaris (PV).Results: PV sera elicited mitochondrial damage, and mitochondria-protecting drugs exhibited protective effect in cell culture and mouse skin.Conclusion: PV antibodies altered O2 respiration, disrupted electron transfer chain, and increased reactive oxygen species.Significance: Results provide the mechanism of therapeutic action and justify the use of mitochondria-protecting drugs in PV.T...

  6. Current research status of radioimmunotherapy monoclonal antibody drug

    International Nuclear Information System (INIS)

    Radioimmunotherapy (RIT) was one of the most important progresses in the field of cancer therapy over the past 20 years. It has been successfully applied in the treatment of blood system tumors such as NHL. For the utilization of RIT in therapy of solid tumors, however, development of more effective monoclonal antibodies, labeling methods and so on are needed. The current status of radionuclides, monoclonal antibodies and drugs commonly used in the RIT were briefly reviewed. (authors)

  7. Cell adhesion molecules: detection with univalent second antibody

    OpenAIRE

    1980-01-01

    Identification of cell surface molecules that play a role in cell-cell adhesion (here called cell adhesion molecules) has been achieved by demonstrating the inhibitory effect of univalent antibodies that bind these molecules in an in vitro assay of cell-cell adhesion. A more convenient reagent, intact (divalent) antibody, has been avoided because it might agglutinate the cells rather than blocking cell-cell adhesion. In this report, we show that intact rabbit immunoglobulin directed against c...

  8. 双特异性单抗对胃肠癌的体内杀伤作用%In vivo killing effect of bispecific single-chain antibody on gastric and colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    刘洪一; 李荣; 刘巨超; 李力; 梁文涛; 钟苑; 徐迎新

    2012-01-01

    Objective To investigate the killing effect of CIK cells mediated by bispecific single - chain antibody, anti - CD3 and anti - CEA, on gastric and colon cancer cells in vivo. Methods Gastric and colon cancer models in nude mice were established after BGC823 cells from human poorly differentiated gastric adenocarcinoma and SW1116 cells from human moderately differentiated colon adenocarcinoma were planted into nude mice. The mice were divided into 3 groups, which were injected with normal saline, CIK cells and CIK cells plus bispecific antibody, respectively, once every 3 days for 6 times. Then the tumors were removed and weighed, and the inhibition rate in each group was calculated. Results Both the CIK cells and CIK cells plus bispecific single - chain antibody could inhibit tumor growth. Inhibition rates of gastric cancer were 29. 90% and 44. 33% respectively. Inhibition rates of colon cancer were 14. 93% and 38. 81% respectively. Compared with CIK cell group, the size and weight of the tumor were significantly smaller in CIK cells plus bispecific singlechain antibody group. Conclusion CIK cells alone can inhibit tumor cell growth and combination of CIK cells and the bispecific single - chain antibody, anti - CD3 and anti - CEA, is more effective in inhibiting tumor growth.%目的 探讨抗CD3抗CEA双特异性单链抗体介导CIK细胞在体内杀伤胃肠癌的作用.方法 分别将人胃低分化腺癌BGC823细胞和人结肠中分化腺癌SW1116细胞种植裸鼠后,建立裸鼠胃癌及肠癌模型,分为3组分别经尾静脉注入生理盐水、CIK细胞及CIK细胞+双特异性单抗,每3天治疗1次,共6次,取出肿瘤组织称重,并计算出各组的抑瘤率.结果 在体内,CIK组和CIK+双抗组均可抑制肿瘤生长,对胃癌的抑瘤率分别为29.90%和44.33%.对结肠癌的抑瘤率分别为14.93%和38.81%.CIK+双抗组:胃癌及结肠癌的瘤体积、瘤重明显小于CIK组.结论 CIK细胞本身可以抑制肿瘤

  9. 抗IL-6R单克隆抗体对脓毒症大鼠的保护机制研究%Protective effects of anti-IL-6R monoclonal antibody in septic rats

    Institute of Scientific and Technical Information of China (English)

    武华栋; 周荣斌

    2011-01-01

    目的 观察抗IL-6受体单克隆抗体(抗IL-6R单抗)干预盲肠结扎穿孔(CLP)脓毒症大鼠的作用,并探讨可能的作用机制.方法 50只Wistar大鼠随机分为五组:假手术组(A组)、CLP+兔IgG 200 μg/kg组(B组)、CLP+IL-6R单抗50 μg/kg组(C组)、CLP+IL-6R单抗100 μg/kg组(D组)、CLP+IL-6R单抗200 μg/kg组(E组),每组10只.观察各组脓毒症大鼠存活率的变化,并使用酶联免疫吸附技术分析各组血清TNF-α、IL-6、IL-17A及IL-21浓度.结果 与B组比较,C、D、E组7 d存活率显著增加(P<0.05),血清TNF-α和IL-6浓度差异无统计学意义,而IL-17A和IL-21浓度则显著减少(P<0.05).结论 抗IL-6R单抗对CLP脓毒症大鼠具有保护作用,该作用可能与Th17细胞受到抑制有关.%Objective To investigate the effects of anti - rat IL - 6R monoclonal antibody in the sepsis model of cecal ligation puncture ( CLP) , and try to find out the potential mechanisms. Methods Fifty female Wista Rats were randomly divided into 5 groups, 10 Rats in each group. The control group was the sham group( group A) . Group B was the model of CLP treated with rabbit IgG ( 200 μg/kg) .Group C, D and E were the model of CLP and were separately treated with anti - rat IL -6R monoclonal antibody 50 μg/kg, 100 μg/kg and 200 μg/kg. Enzyme - linked immunosorbent assay ( ELISA ) was used to detect levels of TNF - α ,IL - 6 , IL - 17A and IL - 21 , and then the survival rates of each group were compared. Results Anti - rat IL - 6R monoclonal antibody treatment resulted in significantly improved survival rate with the increase of dose, the highest dose group had the best survival rate. There was no difference in the concentrations of IL - 6 and TNF - α among the group of treatment with rabbit IgG( group B) and the groups of treatment with anti - rat IL - 6R monoclonal antibody( group C, D and E) . In contrast with group B, the concentrations of IL - 17A and IL - 21 was significantly reduced.Conclusion Protective

  10. Poliarterite nodosa due to anti elastase antibody

    Directory of Open Access Journals (Sweden)

    Caterina Defendenti

    2008-09-01

    Full Text Available The Authors related one case of polyarteritis nodosa occurred to a men forty eight years old.The clinical was characterized by mesenteric and femoral arteries occlusion and chronic cutaneous ulcers to legs. There were bioptical aspects of systemic vasculitis with necrotizing inflammation and a paucity of immune deposit. It was effective oral cyclophosphamide plus steroids. This disease was closely associated with antibodies anti elastase (HLE.The patient had not a history of cocaine abuse or LES disease but the nucleolar pattern ANA was positive >1:640 (anti-nDNA negative. Similar case ANA positive associated with the anti-elastase antibodies, was described by Nassberger (Lancet 1989 for 6/104 patients with LES, anti-nDNA negative. The patient with the highest anti-elastase concentration subsequentely died after very rapid development of severe brain and kidney involvement.

  11. Replacing antibodies with aptamers in lateral flow immunoassay.

    Science.gov (United States)

    Chen, Ailiang; Yang, Shuming

    2015-09-15

    Aptamers have been identified against various targets as a type of chemical or nucleic acid ligand by systematic evolution of ligands by exponential enrichment (SELEX) with high sensitivity and specificity. Aptamers show remarkable advantages over antibodies due to the nucleic acid nature and target-induced structure-switching properties and are widely used to design various fluorescent, electrochemical, or colorimetric biosensors. However, the practical applications of aptamer-based sensing and diagnostics are still lagging behind those of antibody-based tests. Lateral flow immunoassay (LFIA) represents a well established and appropriate technology among rapid assays because of its low cost and user-friendliness. The antibody-based platform is utilized to detect numerous targets, but it is always hampered by the antibody preparation time, antibody stability, and effect of modification on the antibody. Seeking alternatives to antibodies is an area of active research and is of tremendous importance. Aptamers are receiving increasing attention in lateral flow applications because of a number of important potential performance advantages. We speculate that aptamer-based LFIA may be one of the first platforms for commercial use of aptamer-based diagnosis. This review first gives an introduction to aptamer including the selection process SELEX with its focus on aptamer advantages over antibodies, and then depicts LFIA with its focus on aptamer opportunities in LFIA over antibodies. Furthermore, we summarize the recent advances in the development of aptamer-based lateral flow biosensing assays with the aim to provide a general guide for the design of aptamer-based lateral flow biosensing assays. PMID:25912679

  12. Antibody fragments: Hope and hype

    OpenAIRE

    Nelson, Aaron L

    2010-01-01

    The antibody molecule is modular and separate domains can be extracted through biochemical or genetic means. It is clear from review of the literature that a wave of novel, antigen-specific molecular forms may soon enter clinical evaluation. This report examines the developmental histories of therapeutics derived from antigen-specific fragments of antibodies produced by recombinant processes. Three general types of fragments were observed, antigen-binding fragments (Fab), single chain variabl...

  13. The antineutrophil antibody in uveitis.

    OpenAIRE

    Young, D W

    1991-01-01

    Ninety eight patients with uveitis of various types were tested for the presence of the antineutrophil antibody or ANCA by an indirect immunofluorescence method. This antibody is found in patients with diseases associated with small vessel vasculitis, including Wegener's granulomatosis and microscopic polyarteritis. Eleven true positive cases were found. A positive test was not associated with the anatomical site of the uveitis but was related to the time course of the disease. In particular ...

  14. Interfacial metal and antibody recognition

    OpenAIRE

    Zhou, Tongqing; Hamer, Dean H.; Hendrickson, Wayne A.; Sattentau, Quentin J.; Kwong, Peter D.

    2005-01-01

    The unique ligation properties of metal ions are widely exploited by proteins, with approximately one-third of all proteins estimated to be metalloproteins. Although antibodies use various mechanisms for recognition, to our knowledge, none has ever been characterized that uses an interfacial metal. We previously described a family of CD4-reactive antibodies, the archetype being Q425. CD4:Q425 engagement does not interfere with CD4:HIV-1 gp120 envelope glycoprotein binding, but it blocks subse...

  15. Pyoderma gangrenosum and anticardiolipin antibody

    Directory of Open Access Journals (Sweden)

    de Godoy Jose Maria

    2006-01-01

    Full Text Available Pyoderma gangrenosum (PG is a rare ulceronecrotic inflammatory cutaneous disorder and is frequently associated with systemic diseases. The authors report a 22-year-old male patient with pyoderma gangrenosum, thrombosis of both popliteal arteries, ischemic stroke and seropositivity for anticardiolipin antibody. Despite intravenous treatment with antibiotics, corticosteroid and heparin, pyoderma gangrenosum caused necrosis of his right lower limb which resulted in amputation. It was concluded that the anticardiolipin antibody may have contributed to the gravity of this case.

  16. Antibodies to watch in 2014.

    Science.gov (United States)

    Reichert, Janice M

    2014-01-01

    Since 2010, mAbs has documented the biopharmaceutical industry's progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the "Antibodies to watch" series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration's Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed. PMID:24284914

  17. Tabhu: tools for antibody humanization.

    KAUST Repository

    Olimpieri, Pier Paolo

    2014-10-09

    SUMMARY: Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity into a suitable human template. Unfortunately, this procedure may results in a partial or complete loss of affinity of the grafted molecule that can be restored by back-mutating some of the residues of human origin to the corresponding murine ones. This trial-and-error procedure is hard and involves expensive and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps of the humanization experiment protocol. AVAILABILITY: http://www.biocomputing.it/tabhu CONTACT: anna.tramontano@uniroma1.it, pierpaolo.olimpieri@uniroma1.it SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

  18. Radiolabeled monoclonal antibodies: a review

    International Nuclear Information System (INIS)

    Since the description by Kohler and Milstein 1975 of their technique for producing monoclonal antibodies of predefined specificity, it has become a mainstay in most laboratories that utilize immunochemical techniques to study problems in basic, applied or clinical research. Paradoxically, the very success of monoclonal antibodies has generated a literature which is now so vast and scattered that it has become difficult to obtain a perspective. This brief review represents the distillation of many publications relating to the production and use of monoclonaal antibodies as radiopharmaceuticals. Significant advances were made possible in the last few years by combined developments in the fields of tumor-associated antigens and of monoclonal antibodies. In fact monoclonal antibodies against some well defined tumor-associated antigens, has led to significantly greater practical possibilities for producing highly specific radiolabeled antibodies as radiopharmaceuticals for diagnosis and therapy of human tumors. One of the main requirements of this methodology is the availability of stable radiopharmaceutical reagents which after labeling in vivo injection retain the capacity of specific interaction with the defined antigen and their molecular integrity. Since injection into human is the objetive of this kind of study all the specifications of radiopharmaceutical have to be fulfilled e.g. sterility, apirogenicity and absence of toxicity. (author)

  19. Radioimmunoguided surgery using monoclonal antibody

    International Nuclear Information System (INIS)

    The potential proficiency of radioimmunoguided surgery in the intraoperative detection of tumors was assessed using labeled monoclonal antibody B72.3 in 66 patients with tissue-proved tumor. Monoclonal antibody B72.3 was injected 5 to 42 days preoperatively, and the hand-held gamma-detecting probe was used intraoperatively to detect the presence of tumor. Intraoperative probe counts of less than 20 every 2 seconds, or tumor-to-adjacent normal tissue ratios less than 2:1 were considered negative (system failure). Positive probe counts were detected in 5 of 6 patients with primary colon cancer (83 percent), in 31 of 39 patients with recurrent colon cancer (79 percent), in 4 of 5 patients with gastric cancer (80 percent), in 3 of 8 patients with breast cancer (37.5 percent), and in 4 of 8 patients with ovarian cancer (50 percent) undergoing second-look procedures. Additional patients in each group were scored as borderline positive. Overall, radioimmunoguided surgery using B72.3 identified tumors in 47 patients (71.2 percent), bordered on positive in 6 patients (9.1 percent), and failed to identify tumor in 13 patients (19.7 percent). Improved selection of patients for antigen-positive tumors, the use of higher affinity second-generation antibodies, alternate routes of antibody administration, alternate radionuclides, and more sophisticatedly bioengineered antibodies and antibody combinations should all lead to improvements in radioimmunoguided surgery

  20. Monoclonal antibodies technology. Protocols

    International Nuclear Information System (INIS)

    Full text: Immunization. The first step in preparing useful monoclonal antibodies (MAbs) is to immunize an animal (Balb/c for example) with an appropriate antigen. Methods (only for soluble antigen): Solubilize selected antigen in Phosphate buffer solution (PBS) at pH 7.2-7.4, ideally at a final concentration per animal between 10 to 50 μg/ml. It is recommended that the antigen under consideration be incorporated into the emulsion adjuvants in 1:1 volumetric relation. We commonly use Frend's adjuvant (FA) to prepared immunized solution. The first immunization should be prepared with complete FA, and the another could be prepared with incomplete FA. It is recommended to inject mice with 0.2 ml intraperitoneal (ip) or subcutaneous (sc). Our experience suggests the sc route is the preferred route. A minimum protocol for immunizing mice to generate cells for preparing hybridomas is s follows: immunize sc on day 0, boost sc on day 21, take a trial bleeding on day 26; if antibody titters are satisfactory, boost ip on day 35 with antigen only, and remove the spleen to obtain cells for fusion on day 38. Fusion protocol. The myeloma cell line we are using is X63 Ag8.653. At the moment of fusion myeloma cells need a good viability (at least a 95%). 1. Remove the spleen cells from immunized mice using sterile conditions. An immune spleen should yield between 7 a 10x107 nucleated cells. 2. Place the spleen in 20 ml of serum-free RPMI 1640 in a Petri dish. Using a needle and syringe, inject the spleen with medium to distend and disrupt the spleen stroma and free the nucleated cells. 3. Flush the cell suspension with a Pasteur pipet to disperse clumps of cells. 4. Centrifuge the spleen cell suspension at 250g for 10 min. Resuspend the pellet in serum-free RPMI 1640. Determine cell concentration using Neuhabuer chamber. 5. Mix the myeloma cells and spleen cells in a conical 50-ml tube in serum-free RPMI 1640, 1 x107 spleen cells to 1x106 myeloma cells (ratio 10:1). Centrifuge

  1. A Neutralizing Antibody Assay Based on a Reporter of Antibody-Dependent Cell-Mediated Cytotoxicity.

    Science.gov (United States)

    Wu, Yuling; Li, Jia J; Kim, Hyun Jun; Liu, Xu; Liu, Weiyi; Akhgar, Ahmad; Bowen, Michael A; Spitz, Susan; Jiang, Xu-Rong; Roskos, Lorin K; White, Wendy I

    2015-11-01

    Benralizumab is a humanized anti-IL5 receptor α (IL5Rα) monoclonal antibody (mAb) with enhanced (afucosylation) antibody-dependent cell-mediated cytotoxicity (ADCC) function. An ADCC reporter cell-based neutralizing antibody (NAb) assay was developed and characterized to detect NAb against benralizumab in human serum to support the clinical development of benralizumab. The optimal ratio of target cells to effector cells was 3:1. Neither parental benralizumab (fucosylated) nor benralizumab Fab resulted in ADCC activity, confirming the requirement for ADCC activity in the NAb assay. The serum tolerance of the cells was determined to be 2.5%. The cut point derived from normal and asthma serum samples was comparable. The effective range of benralizumab was determined, and 35 ng/mL [80% maximal effective concentration (EC80)] was chosen as the standard concentration to run in the assessment of NAb. An affinity purified goat anti-benralizumab polyclonal idiotype antibody preparation was shown to have NAb since it inhibited ADCC activity in a dose-dependent fashion. The low endogenous concentrations of IL5 and soluble IL5 receptor (sIL5R) did not demonstrate to interfere with the assay. The estimated assay sensitivities at the cut point were 1.02 and 1.10 μg/mL as determined by the surrogate neutralizing goat polyclonal and mouse monoclonal anti-drug antibody (ADA) controls, respectively. The assay can detect NAb (at 2.5 μg/mL) in the presence of 0.78 μg/mL benralizumab. The assay was not susceptible to non-specific matrix effects. This study provides an approach and feasibility of developing an ADCC cell-based NAb assay to support biopharmaceuticals with an ADCC function. PMID:26205082

  2. Antiphospholipid Antibodies in Lupus Nephritis.

    Science.gov (United States)

    Parodis, Ioannis; Arnaud, Laurent; Gerhardsson, Jakob; Zickert, Agneta; Sundelin, Birgitta; Malmström, Vivianne; Svenungsson, Elisabet; Gunnarsson, Iva

    2016-01-01

    Lupus nephritis (LN) is a major manifestation of systemic lupus erythematosus (SLE). It remains unclear whether antiphospholipid antibodies (aPL) alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204) or without (n = 294) LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous), before and after induction treatment (short-term outcomes). Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR) and the Chronic Kidney Disease (CKD) stage, after a median follow-up of 11.3 years (range: 3.3-18.8). Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all), but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1-2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are affected by

  3. Antiphospholipid Antibodies in Lupus Nephritis.

    Directory of Open Access Journals (Sweden)

    Ioannis Parodis

    Full Text Available Lupus nephritis (LN is a major manifestation of systemic lupus erythematosus (SLE. It remains unclear whether antiphospholipid antibodies (aPL alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204 or without (n = 294 LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous, before and after induction treatment (short-term outcomes. Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR and the Chronic Kidney Disease (CKD stage, after a median follow-up of 11.3 years (range: 3.3-18.8. Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all, but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1-2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are

  4. Tumor-penetrating peptide fused EGFR single-domain antibody enhances cancer drug penetration into 3D multicellular spheroids and facilitates effective gastric cancer therapy

    Science.gov (United States)

    Sha, Huizi; Zou, Zhengyun; Xin, Kai; Bian, Xinyu; Cai, Xueting; Lu, Wuguang; Chen, Jiao; Chen, Gang; Huang, Leaf; Blair, Andrew M.; Cao, Peng; Liu, Baorui

    2016-01-01

    Human tumors, including gastric cancer, frequently express high levels of epidermal growth factor receptors (EGFRs), which are associated with a poor prognosis. Targeted delivery of anticancer drugs to cancerous tissues shows potential in sparing unaffected tissues. However, it has been a major challenge for drug penetration in solid tumor tissues due to the complicated tumor microenvironment. We have constructed a recombinant protein named anti-EGFR-iRGD consisting of an anti-EGFR VHH (the variable domain from the heavy chain of the antibody) fused to iRGD, a tumor-specific binding peptide with high permeability. Anti-EGFR-iRGD, which targets EGFR and αvβ3, spreads extensively throughout both the multicellular spheroids and the tumor mass. The recombinant protein anti-EGFR-iRGD also exhibited antitumor activity in tumor cell lines, multicellular spheroids, and mice. Moreover, anti-EGFR-iRGD could improve anticancer drugs, such as doxorubicin (DOX), bevacizumab, nanoparticle permeability and efficacy in multicellular spheroids. This study draws attention to the importance of iRGD peptide in the therapeutic approach of anti-EGFR-iRGD. As a consequence, anti-EGFR-iRGD could be a drug candidate for cancer treatment and a useful adjunct of other anticancer drugs. PMID:25553823

  5. [Anti-basal ganglia antibody].

    Science.gov (United States)

    Hayashi, Masaharu

    2013-04-01

    Sydenham's chorea (SC) is a major manifestation of rheumatic fever, and the production of anti-basal ganglia antibodies (ABGA) has been proposed in SC. The pathogenesis is hypothesized as autoimmune targeting of the basal ganglia via molecular mimicry, triggered by streptococcal infection. The spectrum of diseases in which ABGA may be involved has been broadened to include other extrapyramidal movement disorders, such as tics, dystonia, and Parkinsonism, as well as other psychiatric disorders. The autoimmune hypothesis in the presence and absence of ABGA has been suggested in Tourette's syndrome (TS), early onset obsessive-compulsive disorders (OCD), and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Recently, the relationship between ABGA and dopamine neurons in the basal ganglia has been examined, and autoantibodies against dopamine receptors were detected in the sera from patients with basal ganglia encephalitis. In Japan, the occurrence of subacute encephalitis, where patients suffer from episodes of altered behavior and involuntary movements, has increased. Immune-modulating treatments are effective, indicating the involvement of an autoimmune mechanism. We aimed to detect the anti-neuronal autoantibodies in such encephalitis, using immunohistochemical assessment of patient sera. The sera from patients showing involuntary movements had immunoreactivity for basal ganglia neurons. Further epitopes for ABGA will be investigated in basal ganglia disorders other than SC, TS, OCD, and PANDAS. PMID:23568985

  6. 党参粗提物对免疫青脚麻鸡血清抗体效价的影响%Effects of Lanceolata on the Serum Antibody Titer in Immune Cyan- shank Partridge Chicken

    Institute of Scientific and Technical Information of China (English)

    杨崤松; 董媛艳; 宁康健

    2012-01-01

    To observe the effects of Lanceolata crude extract with different concentration on the serum antibody ti- ter of Newcastle disease(ND) and Infections bursal disease(IBD) in Cyan - shank partridge chickens, 400 one day Cyan - shank partridge chichens were divided into four groups at random (50 per repetition). The dosages of Lanceolata crude extract in I - 1Vgroups drinking water were respectively 0, 0.5, 1.0 and 2.0g/L from four- teen days old fed on Lanceolata for six weeks, ND and IBD antigen routine immunization. At each weekend, eight chickens were taken respectly in each group, from heart we picked the blood and separated the serum, and then serum antibody titer of ND and IBD were determined with Newcastle Hemagglutination Inhibition (ND - HI) and Agar Diffusion Experiment(ADE) respectively. The result showed that the ND -HI antibody titer from 28 days old and IBD antibody titer in Lanceolata groups were highter 1 to 2 titer than control group from 35 days old. It indicates that the adding Lanceolata crude extract can improve serum antibody titer of ND and IBD in Cyan - shank partridge chickens and moderate dose is better.%观察不同浓度的党参粗提物对青脚麻鸡血清中新城疫(ND)及传染性法氏囊炎(IBD)抗体效价的影响。400只1日龄青脚麻鸡随机均分4组,I-Ⅳ组分别在饮水中添加0g/L、0.5g/L、lg/L和2g/L的党参粗提物,14日龄开始给药,连续饮用6周,正常鸡新城疫和传染性法氏囊免疫。每周末各组随机抽样8只,心脏采血,分离血清,用微量血凝抑制实验(HI)测定ND抗体效价,琼脂扩散实验测定IBD抗体效价。结果表明,血清ND-HI抗体效价自28日龄起,IBD琼扩效价自35日龄起,党参各组较对照组均高出1-2个滴度以上,说明添加党参粗提物能够提高青脚麻鸡血清中ND-HI和IBD的抗体效价,其中中剂量药效为佳。

  7. Engineered Antibodies for Monitoring of Polynuclear Aromatic Hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Alexander E. Karu Ph.D; Victoria A. Roberts Ph.D.; Qing X. Li, Ph.D.

    2002-01-17

    This project was undertaken to fill needs in ODE's human and ecosystem health effects research, site remediation, rapid emergency response, and regulatory compliance monitoring programs. Doe has greatly stimulated development and validation of antibody-based, rapid, field-portable detection systems for small hazardous compounds. These range from simple dipsticks, microplate enzyme-linked immunosorbent assays (ELISAs), and hand-held colorimeters, to ultrasensitive microfluidic reactors, fiber-optic sensors and microarrays that can identify multiple analytes from patterns of cross-reactivity. Unfortunately, the technology to produce antibodies with the most desirable properties did not keep pace. Lack of antibodies remains a limiting factor in production and practical use of such devices. The goals of our project were to determine the chemical and structural bases for the antibody-analyte binding interactions using advanced computational chemistry, and to use this information to create useful new binding properties through in vitro genetic engineering and combinatorial library methods.

  8. Determination of Al, Cd, Cu, Fe in 111InCl3 radiopharmaceuticals solutions by flameless atomic absorption spectrometry: results and effects on 111In labelling of monoclonal antibodies

    International Nuclear Information System (INIS)

    Determination of trace elements in 111InCl3 solution have been carried out by flameless atomic absorption spectrometry. Five successive batches from three European companies have been analysed. The means of measured values range from 4560 to 6930 μ g L-1 for aluminium, 131 to 874 for cadmium, 49 to 300 for copper, 387 to 698 for iron. Using two molar ratio indexes, trivalent metallic traces have been compared to theoretical 111In content. The trace elements largely exceed radioactive material. As Fe and In have similar chemical properties, it results in low specific activity of radioactive complex when labeling monoclonal antibodies by 111In. Using a mathematical model, a detrimental effect of Fe trace levels has been studied. (author)

  9. Antibody Derived Peptides for Detection of Ebola Virus Glycoprotein.

    Directory of Open Access Journals (Sweden)

    Luis Mario Rodríguez-Martínez

    Full Text Available Current Ebola virus (EBOV detection methods are costly and impractical for epidemic scenarios. Different immune-based assays have been reported for the detection and quantification of Ebola virus (EBOV proteins. In particular, several monoclonal antibodies (mAbs have been described that bind the capsid glycoprotein (GP of EBOV GP. However, the currently available platforms for the design and production of full-length mAbs are cumbersome and costly. The use of antibody fragments, rather than full-length antibodies, might represent a cost-effective alternative for the development of diagnostic and possibly even therapeutic alternatives for EBOV.We report the design and expression of three recombinant anti-GP mAb fragments in Escherichia coli cultures. These fragments contained the heavy and light variable portions of the three well-studied anti-GP full-length mAbs 13C6, 13F6, and KZ52, and are consequently named scFv-13C6, scFv-13F6, and Fab-KZ52, respectively. All three fragments exhibited specific anti-GP binding activity in ELISA experiments comparable to that of full-length anti-GP antibodies (i.e., the same order of magnitude and they are easily and economically produced in bacterial cultures.Antibody fragments might represent a useful, effective, and low cost alternative to full-length antibodies in Ebola related capture and diagnostics applications.

  10. Fluorescent labeling of antibody fragments using split GFP.

    Directory of Open Access Journals (Sweden)

    Fortunato Ferrara

    Full Text Available Antibody fragments are easily isolated from in vitro selection systems, such as phage and yeast display. Lacking the Fc portion of the antibody, they are usually labeled using small peptide tags recognized by antibodies. In this paper we present an efficient method to fluorescently label single chain Fvs (scFvs using the split green fluorescent protein (GFP system. A 13 amino acid tag, derived from the last beta strand of GFP (termed GFP11, is fused to the C terminus of the scFv. This tag has been engineered to be non-perturbing, and we were able to show that it exerted no effect on scFv expression or functionality when compared to a scFv without the GFP11 tag. Effective functional fluorescent labeling is demonstrated in a number of different assays, including fluorescence linked immunosorbant assays, flow cytometry and yeast display. Furthermore, we were able to show that this split GFP system can be used to determine the concentration of scFv in crude samples, as well an estimate of antibody affinity, without the need for antibody purification. We anticipate this system will be of widespread interest in antibody engineering and in vitro display systems.

  11. Natural hidden antibodies reacting with DNA or cardiolipin bind to thymocytes and evoke their death.

    Science.gov (United States)

    Zamulaeva, I A; Lekakh, I V; Kiseleva, V I; Gabai, V L; Saenko, A S; Shevchenko, A S; Poverenny, A M

    1997-08-18

    Both free and hidden natural antibodies to DNA or cardiolipin were obtained from immunoglobulins of a normal donor. The free antibodies reacting with DNA or cardiolipin were isolated by means of affinity chromatography. Antibodies occurring in an hidden state were disengaged from the depleted immunoglobulins by ion-exchange chromatography and were then affinity-isolated on DNA or cardiolipin sorbents. We used flow cytometry to study the ability of free and hidden antibodies to bind to rat thymocytes. Simultaneously, plasma membrane integrity was tested by propidium iodide (PI) exclusion. The hidden antibodies reacted with 65.2 +/- 10.9% of the thymocytes and caused a fast plasma membrane disruption. Cells (28.7 +/- 7.1%) were stained with PI after incubation with the hidden antibodies for 1 h. The free antibodies bound to a very small fraction of the thymocytes and did not evoke death as compared to control without antibodies. The possible reason for the observed effects is difference in reactivity of the free and hidden antibodies to phospholipids. While free antibodies reacted preferentially with phosphotidylcholine, hidden antibodies reacted with cardiolipin and phosphotidylserine. PMID:9280287

  12. Antithyroid antibodies and thyroid function in pediatric patients with celiac disease.

    Science.gov (United States)

    Kalyoncu, Derya; Urganci, Nafiye

    2015-01-01

    Objective. Aim of the study was to determine the prevalence of autoimmune thyroid disease, persistence of antithyroid antibodies, effect of gluten-free diet, and long-term outcome of thyroid function in pediatric patients with celiac disease (CD). Methods. 67 patients with CD aged from 1 year to 16 years were screened for thyroid antithyroperoxidase, antithyroglobulin and anti-TSH receptor antibodies, serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone (TSH) at diagnosis and during follow-up. Results. None of the patients had antithyroid antibodies at diagnosis. Antithyroid antibodies became positive in 16.4% of the patients (11/67) 2 to 3 years after the diagnosis of CD. Clinical hypothyroidism was observed only in 3 of 11 CD patients with positive antithyroid antibodies (27.2%). The antithyroid antibodies positive and negative patients did not differ significantly according to compliance to GFD (P > 0.05). A statistically significant difference was observed only in age, in which the patients with positive antithyroid antibodies were younger than the patients with negative antithyroid antibodies (P = 0.004). None of the patients had any change in their thyroid function and antibody profile during their follow-up. Conclusion. Antithyroid antibodies were detected in younger pediatric patients with CD and the prevalence of antithyroid antibodies did not correlate with the duration of gluten intake. PMID:25788942

  13. Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells

    International Nuclear Information System (INIS)

    A chimeric mouse-human antibody has been created that recognizes an antigen found on the surface of cells from many carcinomas. Immunoglobulin constant (C) domains of the mouse monoclonal antibody L6, C/sub γ2a/ and C/sub kappa/, were substituted by the human C/sub γ1/ and C/sub kappa/ by recombining cDNA modules encoding variable or C domains. The cDNA constructs were transfected into lymphoid cells for antibody production. The chimeric antibody and mouse L6 antibody bound to carcinoma cells with equal affinity and mediated complement-dependent cytolysis. In the presence of human effector cells, the chimeric antibody gave antibody-dependent cellular cytotoxicity at 100 times lower concentration than that needed for the mouse L6 antibody. The assay for lysis was carried out with 51Cr-labeled target calls. The chimeric antibody, but not the mouse L6 antibody, is effective against a melanoma line expressing small amounts of the L6 antigen. The findings point to the usefulness of the chimeric antibody approach for obtaining agents with strong antitumor activity for possible therapeutic use in man

  14. Production of recombinant antibodies using bacteriophages

    OpenAIRE

    Shukra, A. M.; Sridevi, N. V.; Dev Chandran,; Kapil Maithal,

    2014-01-01

    Recombinant antibody fragments such as Fab, scFv, diabodies, triabodies, single domain antibodies and minibodies have recently emerged as potential alternatives to monoclonal antibodies, which can be engineered using phage display technology. These antibodies match the strengths of conventionally produced monoclonal antibodies and offer advantages for the development of immunodiagnostic kits and assays. These fragments not only retain the specificity of the whole monoclonal ...

  15. Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection.

    Science.gov (United States)

    Pleass, Richard J; Ogun, Solabomi A; McGuinness, David H; van de Winkel, Jan G J; Holder, Anthony A; Woof, Jenny M

    2003-12-15

    Parasite drug resistance and difficulties in developing effective vaccines have precipitated the search for alternative therapies for malaria. The success of passive immunization suggests that immunoglobulin (Ig)-based therapies are effective. To further explore the mechanism(s) by which antibody mediates its protective effect, we generated human chimeric IgG1 and IgA1 and a single-chain diabody specific for the C-terminal 19-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP119), a major target of protective immune responses. These novel human reagents triggered in vitro phagocytosis of merozoites but, unlike their parental mouse IgG2b, failed to protect against parasite challenge in vivo. Therefore, the Fc region appears critical for mediating protection in vivo, at least for this MSP119 epitope. Such antibodies may serve as prototype therapeutic agents, and as useful tools in the development of in vitro neutralization assays with Plasmodium parasites. PMID:12855589

  16. Antibody purification using affinity chromatography: a case study with a monoclonal antibody to ractopamine.

    Science.gov (United States)

    Wang, Zhanhui; Liang, Qi; Wen, Kai; Zhang, Suxia; Shen, Jianzhong

    2014-11-15

    The application of antibodies to small molecules in the field of bioanalytics requires antibodies with stable biological activity and high purity; thus, there is a growing interest in developing rapid, inexpensive and effective procedures to obtain such antibodies. In this work, a ractopamine (RAC) derivative, N-4-aminobutyl ractopamine (ABR), was synthesized for preparing new specific affinity chromatography to purify a murine monoclonal antibody (mAb) against RAC from ascites. The performance of the new specific chromatography was compared with four other purification methods in terms of recovery, purity and biological activity of mAb. These four purification methods were prepared by using specific ligands (RAC and RAC-ovalbumin) and commercial ligands (protein G and protein A), respectively. The results showed that the highest recovery (88.1%) was achieved using the new chromatography; in comparison, the recoveries from the other methods were all below 70%. The purity of the mAbs from the new chromatography was 88.3%, while, the highest purity of 97.6% was from protein G chromatography and the lowest purity of 84.7% was from protein A chromatography. The biological activity of the purified mAb from all of the chromatography methods was comparable in enzyme-linked immunosorbent immunoassay (ELISA). PMID:25261834

  17. Fc-galactosylation modulates antibody-dependent cellular cytotoxicity of therapeutic antibodies.

    Science.gov (United States)

    Thomann, Marco; Reckermann, Katharina; Reusch, Dietmar; Prasser, Jessica; Tejada, Max L

    2016-05-01

    The therapeutic activity of monoclonal antibodies can involve immune cell mediated effector functions including antibody-dependent cellular cytotoxicity (ADCC), an activity that is modulated by the structure of Fc-glycans, and in particular the lack of core fucose. The heterogeneity of these glycostructures and the inherent variability of traditional PBMC-based in vitro ADCC assays, have made it challenging to quantitatively assess the impact of other glycostructures on ADCC activity. We applied a quantitative NK cell based assay to generate a database consisting of Fc-glycostructure and ADCC data from 54 manufacturing batches of a CHO-derived monoclonal antibody. Explorative analysis of the data indicated that, apart from afucosylation, galactosylation levels could influence ADCC activity. We confirmed this hypothesis by demonstrating enhanced ADCC upon enzymatic hypergalactosylation of four different monoclonal antibodies derived using standard CHO manufacturing processes. Furthermore we quantitatively compare the effects of galactosylation and afucosylation in the context of glycan heterogeneity and demonstrate that while galactose can influence ADCC activity, afucosylation remains the primary driver of this activity. PMID:27058641

  18. Therapeutic effects of antigen affinity-purified polyclonal anti-receptor of advanced glycation end-product (RAGE) antibodies on cholestasis-induced liver injury in rats.

    Science.gov (United States)

    Xia, Peng; Deng, Qing; Gao, Jin; Yu, Xiaolan; Zhang, Yang; Li, Jingjing; Guan, Wen; Hu, Jianjun; Tan, Quanhui; Zhou, Liang; Han, Wei; Yuan, Yunsheng; Yu, Yan

    2016-05-15

    Cholestasis leads to acute hepatic injury, fibrosis/cirrhosis, inflammation, and duct proliferation. We investigated whether blocking receptor of advanced glycation end-products (RAGE) with polyclonal anti-RAGE antibodies (anti-RAGE) could regulate acute liver injury and fibrosis in a rat bile duct ligation (BDL) model. Male Wister rats received 0.5mg/kg rabbit anti-RAGE or an equal amount of rabbit IgG by subcutaneous injection twice a week after BDL. Samples of liver tissue and peripheral blood were collected at 14 days after BDL. Serum biochemistry and histology were used to analyze the degree of liver injury. Quantitative real-time PCR (qPCR) and immunohistochemical staining were used to further analyze liver injury. Anti-RAGE improved the gross appearance of the liver and the rat survival rate. Liver tissue histology and relevant serum biochemistry indicated that anti-RAGE attenuated liver necrosis, inflammation, liver fibrosis, and duct proliferation in the BDL model. qPCR and western blotting showed significant reductions in interleukin-1β expression levels in the liver by treatment with anti-RAGE. Anti-RAGE also significantly reduced the mRNA levels of α1(1) collagen (Col1α1) and cholesterol 7α-hydroxylase, and the ratio of tissue inhibitor of matrix metalloproteinase-1 to matrix metalloproteinases (MMPs) in the liver. In addition, anti-RAGE regulated the transcriptional level of Col1α1 and MMP-9 in transforming growth factor-β-induced activated LX-2 cells in vitro. Anti-RAGE was found to inhibit hepatic stellate cell proliferation in vivo and in vitro. Therefore, anti-RAGE can protect the liver from injury induced by BDL in rats. PMID:26970185

  19. Changes in the Properties of the Thyrotropin Receptor Antibody in Patients with Graves’ Disease after Radioiodine Treatment

    OpenAIRE

    Cho, Bo Youn; Shong, Young Kee; Chung, June-Key; Lee, Myung Chul; Lee, Hong Kyu; Koh, Chang-Soon; Min, Hun Ki

    1990-01-01

    We investigated the effect of a single dose of 131I upon thyrotropin receptor antibodies (TRAb) in 21 patients with Graves’ disease. The thyrotropin receptor antibodies were assessed by parallel measurements of thyrotropin binding inhibitor immunoglobulin (TBII), thyroid stimulating antibody (TSAb) and thyroid stimulation blocking antibody (TSBAb) in serum by radoreceptor assay, stimulation of adenlate cyclase and inhibition of TSH-stimulated adenylate cyclase activation in FRTL-5 cells, resp...

  20. Antibodies to watch in 2016.

    Science.gov (United States)

    Reichert, Janice M

    2016-01-01

    The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, are projected to gain first approvals in 2016. Commercial late-stage antibody therapeutics development exceeded expectations by increasing from 39 candidates in Phase 3 studies as of late 2014 to 53 as of late 2015. Of the 53 candidates, transitions to regulatory review by the end of 2016 are projected for 8 (atezolizumab, benralizumab, bimagrumab, durvalumab, inotuzumab ozogamicin, lebrikizumab, ocrelizumab, tremelimumab). Other "antibodies to watch" include 15 candidates (bavituximab, bococizumab, dupilumab, fasinumab, fulranumab, gevokizumab, guselkumab, ibalizumab, LY2951742, onartuzumab, REGN2222, roledumab, romosozumab, sirukumab, Xilonix) undergoing evaluation in Phase 3 studies that have estimated primary completion dates in 2016. As evidenced by the antibody therapeutics discussed in this perspective, the biopharmaceutical industry has a highly active late-stage clinical pipeline that may deliver numerous new products to the global market in the near future. *See Note added in proof for updates through December 31, 2015. PMID:26651519